Sarah Yeo, Stephen Q Wong, Farzaneh Atashrazm, Andreas Behren, Anthony T Papenfuss, Natalia Vukelic, Lisa Briggs, Ashleigh R Poh, Daniel Steinfort, Natasha Smallwood, Kate Sutherland, Vivek Naranbhai, Sagun Parakh, Tracy Leong
{"title":"澳大利亚的肺癌生物银行:挑战和未来方向。","authors":"Sarah Yeo, Stephen Q Wong, Farzaneh Atashrazm, Andreas Behren, Anthony T Papenfuss, Natalia Vukelic, Lisa Briggs, Ashleigh R Poh, Daniel Steinfort, Natasha Smallwood, Kate Sutherland, Vivek Naranbhai, Sagun Parakh, Tracy Leong","doi":"10.5694/mja2.70012","DOIUrl":null,"url":null,"abstract":"<p>Lung cancer is the leading cause of cancer-related morbidity and mortality worldwide.<span><sup>1</sup></span> It is the fifth most common cancer diagnosed in Australia, but accounts for almost 20% of all cancer-related deaths, which is more than breast, prostate and ovarian cancer combined. Global advances in lung cancer management have been driven by early diagnosis, such as lung cancer screening, improved treatment options (targeted therapy and immunotherapy) and improvements in survivorship care. Despite this progress, the five-year survival rate for lung cancer in Australia is 24%.<span><sup>2</sup></span> Reasons for this poor outlook include late presentation with most lung cancer patients presenting with metastatic disease at the time of diagnosis, as well as tumour-specific features including a lack of reliable biomarkers, tumour heterogeneity and drug resistance.<span><sup>3</sup></span></p><p>Lung cancer biobanks facilitate translational research aimed at improving lung cancer diagnosis, prognosis and treatment in several ways.<span><sup>4</sup></span> These repositories collect and store high quality biological samples, such as tissue and blood, as well as detailed clinical information from patients across various stages of disease. This enables researchers to identify and validate predictive and prognostic biomarkers, discover molecular signatures associated with tumour progression and treatment resistance, and develop novel therapies and strategies to overcome resistance.<span><sup>5</sup></span></p><p>This perspective article provides a background on cancer biobanks, outlines the challenges specific to lung cancer biobanks in the Australian context, and discusses future directions.</p><p>Biobanks are defined by the Organisation for Economic Co-operation and Development as “a structured resource that can be used for the purpose of genetic research and which include: (a) human biological materials and/or information generated from the analysis of the same; and (b) extensive associated information”.<span><sup>6</sup></span> Cancer-focused biobanks are invaluable collections of biological specimens accompanied by matched health and demographic data. The International Agency for Research on Cancer states that biobanks underpin three rapidly expanding research fields aimed at developing effective strategies to prevent, diagnose and treat cancer: molecular and genetic epidemiology to assess the genetic and environmental bases of cancer; molecular pathology to develop molecular-based classifications and further phenotyping of different cancers; and pharmacogenomics/pharmaco–proteomics to understand the correlation between a patient's genotype/phenotype and their response to drug treatment.<span><sup>7</sup></span></p><p>With the assistance of a medical librarian, a search of Ovid MEDLINE(R) ALL 1946 to 4 April 2025 was conducted using a combination of MeSH headings and keywords containing “lung cancer” and “biobank” (search strategy provided in Supporting Information). There were 488 abstracts identified and screened, resulting in 379 relevant records. Of these, most (316) referred to research conducted using the UK Biobank, underscoring the importance of the UK Biobank in research and clinical contexts. Other cited biobanks included FinnGen (Finland) and China Kadoorie Biobank (China). Very few lung cancer-specific biobanks were identified, as summarised in Box 1.</p><p>Of the lung cancer biobanks described in Box 1, the only biobank currently collecting specimens, as well as being open for researchers’ applications is the Lung Biobank in Heidelberg, which has been operating for over 20 years with 16 000 patient specimens (with most specimens collected from people with lung cancer). Other lung cancer biobanks, such as the Shanghai Chest Hospital Lung Cancer Biobank, the Lung Cancer Biobank Nice and the European Early Lung Cancer Biobank, are no longer collecting specimens, and there is no clear online application pathway for researchers to apply to conduct research on collected specimens. Of these lung cancer biobanks, most lung cancer specimens are from surgical resections, which is concerning as most people with lung cancer have metastatic, unresectable disease, therefore the research produced from resected specimens may not be as relevant.</p><p>Australia is home to several well established pan-cancer biobanks as well as tumour-specific biobanks, but lung cancer biobanking in Australia is in its infancy. An example of an Australian cancer-agnostic biobank is the Victorian Cancer Biobank — which holds over 460 000 biospecimens — and provides access to samples collected in Victoria for approved research projects. The Victorian Cancer Biobank includes lung cancer specimens and as of April 2025, its catalogue listed lung cancer resection specimens from more than 50 donors and four metastatic lymph node specimens from two donors with advanced lung cancer.<span><sup>15</sup></span> There are also Australian cancer-specific biobanks, such as the Melanoma Institute Australia Biospecimen Bank, the Australian Breast Cancer Tissue Bank, and Brain Cancer Biobanking Australia. In addition, the new TRACKER (Tissue Repository of Airway Cancers for Knowledge Expansion of Resistance) lung cancer biobank is a consumer-partnered initiative focused on lung cancer.<span><sup>16</sup></span> TRACKER stores longitudinal biospecimens (including tumour tissue, peripheral blood and bronchoalveolar lavage fluid [BALF]) at diagnosis, during therapy and at disease progression.</p><p>Traditionally, lung cancer tissue for biobanking has been acquired through surgical resection of early-stage tumours, as this method provides large samples suitable for analysis. However, surgical biopsies are not representative of tumours in most individuals diagnosed with lung cancer, as most patients present with metastatic disease, which is inoperable.<span><sup>17</sup></span> Tissue acquisition from metastatic sites is often complex due to anatomical inaccessibility or patient-related factors and, as such, staging metastatic lung cancer can be challenging.<span><sup>18</sup></span> An example of a challenging metastatic site is the brain, which is difficult to obtain samples from without resection and usually carries high peri-operative risk. Similarly, liver and adrenal biopsies pose risks such as bleeding or bile leakage due to proximity to vascular structures, whereas bone biopsies are often painful and may not yield sufficient tissue for diagnosis.</p><p>Often the most practical methods for obtaining tissue for both diagnostic and biobanking purposes are minimally invasive bronchoscopic techniques such as linear endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for accessible nodal disease, and computed tomography-guided lung biopsies for direct sampling of lung lesions. Cytological specimens obtained from linear EBUS-TBNA procedures have been shown to provide adequate DNA yields for molecular analyses, including targeted and whole exome sequencing.<span><sup>19</sup></span> It is well established that the tumour microenvironment varies depending on anatomical site of disease.<span><sup>20</sup></span> Therefore, to facilitate the study of heterogenous responses to treatment, a biobank should include a range of anatomical samples.</p><p>Longitudinal sampling is crucial in lung cancer research due to the dynamic nature of biomarkers (eg, programmed death ligand-1; PD-L1), which vary both spatially (depending on the biopsy site) and temporally (changing throughout treatment). As immunotherapy efficacy is closely linked to PD-L1 expression levels, understanding resistance mechanisms necessitates repeated tissue sampling across different treatment phases. Minimally invasive procedures, such as EBUS-TBNA, allow for longitudinal sampling and can provide invaluable insights into tumour evolution, resistance mechanisms and patient-specific responses to therapies.<span><sup>8</sup></span></p><p>A key challenge with longitudinal sampling is the ethical and clinical concern of subjecting patients to repeated procedures purely for research purposes, which may increase patient risk and compromise ethical standards. When tissue is required for multiple purposes, including: (i) diagnosis; (ii) molecular analysis to guide treatment decisions; (iii) biobanking for future research; and (iv) eligibility for clinical trial enrolment, a single sample may not be sufficient to meet all these demands. Engaging with organisations that can facilitate access to archived tissue samples, or through participation in national networks, such as Lung Foundation Australia, the Thoracic Oncology Group Australasia, the Thoracic Society of Australia and New Zealand, and the Australian Registry and Biobank of Thoracic Cancers, allows for research collaboration, which may improve analysis methods so more can be done with less tissue.</p><p>Blood-based liquid biopsies offer a less invasive alternative for tracking circulating tumour DNA throughout the course of treatment, enabling monitoring of genomic alterations associated with therapy resistance.<span><sup>21</sup></span> Measuring circulating tumour DNA to assess tumour response is particularly valuable in lung cancer, where repeat tissue biopsies are often impractical. This approach allows for more refined prognostic assessments, tailored surveillance intervals and informed adjustments to therapy. Biobanks that collect a variety of lung cancer biospecimens longitudinally will be critical for translational research, helping to drive the development of personalised treatment strategies based on dynamic molecular profiling.</p><p>Translational research using biobanked lung cancer specimens encompasses a range of analytical approaches. These include genomic analysis (eg, identifying mutations such as in epidermal growth factor receptor [<i>EGFR</i>]), transcriptomic profiling (eg, assessing PD-L1 expression, which can correlate with immunotherapy response), and microbiome studies (eg, understanding how gut bacteria influence treatment outcomes). When these layers of data are combined, the approach is referred to as multi-omics, enabling comprehensive molecular profiling that supports the development of personalised treatment strategies tailored to the evolving nature of an individual's disease.</p><p>Integrating multi-omic data provides deeper insights into resistance mechanisms. This strategy can identify predictive biomarkers for systemic therapies as well as potential applications in surgical and radiotherapy interventions in future studies.</p><p>Internationally, efforts in achieving proportional ethnic diversity in biobanks have been driven by legislation, such as: (i) setting recruitment guidelines from the outset to ensure diversity and developing culturally competent guidelines for researchers; (ii) establishing ethnic diversity recruitment subgroups to broaden participation; and (iii) creating culturally informed research frameworks. In contrast, Australia lacks a legislative framework to guide the inclusion of Indigenous peoples and other ethnically diverse populations in biobanks or biomedical research.<span><sup>22</sup></span> Additional barriers for these priority populations, particularly Indigenous communities, include concerns surrounding the collection, storage and use of biological specimens, as well as uncertainties related to data sharing and ownership rights. Research involving Indigenous Australians must adapt study protocols to respect cultural values, address community priorities, ensure meaningful community consultation and include Indigenous researchers.<span><sup>23</sup></span></p><p>To enhance the relevance and impact of biobanks in health and medical research, it is vital to engage with patients, caregivers and consumer advocates. The stakeholder insights and feedback help shape study design, while participant information and consent processes ensure that research is patient-centred and reflective of real-world needs. Their involvement also strengthens advocacy efforts and recruitment strategies, fostering broader community trust and participation in research initiatives. By prioritising consumer engagement, we can build a research environment that authentically reflects the experiences and priorities of those it seeks to benefit.</p><p>Despite increasing efforts to support inclusive participation, significant gaps remain. There is a lack of diversity among consumers involved in research, echoing similar challenges seen in the composition of biobanked specimens. Priority populations — including populations with lower levels of health literacy, education and socio-economic status — continue to be under-represented.<span><sup>24</sup></span> This disparity persists despite the existence of national frameworks such as the National Framework for Consumer Involvement in Cancer Control.<span><sup>25</sup></span></p><p>The translational potential of biobanks depends on access to researchers who can effectively use these biospecimens for high quality analyses and publication in peer-reviewed journals, with the goal to improve outcomes of people with lung cancer (Box 2).</p><p>Despite considerable advances in lung cancer management, significant challenges remain in improving patient outcomes. High quality, long term, consumer-partnered lung cancer biobanks are critical to advancing the necessary translational research.</p><p>The development of large, clinically annotated, multi-omic datasets from lung cancer patients will provide essential insights into predictive and prognostic biomarkers and identify novel therapeutic targets to overcome resistance and improve treatment responses. Enhancing patient selection for clinical trials and identifying new agents to target resistance mechanisms may enable more personalised therapies. This will facilitate the design of synergistic combination strategies for treatment-refractory patients.</p><p>Reducing treatment resistance will ultimately lead to better clinical outcomes, improved survival and enhanced quality of life for patients with lung cancer. Lung cancer biobanking is a crucial step in building the infrastructure needed to enable access to biospecimens and associated multi-omic and clinical data for researchers both nationally and internationally. This will increase research efficiency, reduce costs and, most importantly, foster greater collaboration, all with the goal of improving the lives and outcomes of people affected by cancer.</p><p>Open access publishing facilitated by The University of Melbourne, as part of the Wiley - The University of Melbourne agreement via the Council of Australian University Librarians.</p><p>No relevant disclosures.</p><p>Not commissioned; externally peer reviewed.</p><p>Yeo S: Investigation, methodology, visualization, writing - original draft, writing - review and editing. Wong SQ: Writing - review and editing. Atashrazm F: Resources, writing - review and editing. Behren A: Conceptualization, writing - review and editing. Papenfuss AT: Writing - review and editing. Vukelic N: Project administration, resources, writing - original draft, writing - review and editing. Briggs L: Conceptualization, writing - review and editing. Poh AR: Writing - review and editing. Steinfort D: Supervision, writing - review and editing. Smallwood N: Supervision, writing - review and editing. Sutherland K: Supervision, writing - review and editing. Naranbhai V: Supervision, writing - review and editing. Parakh S: Conceptualization, supervision, writing - original draft, writing - review and editing. Leong T: Conceptualization, supervision, writing - original draft, writing - review and editing.</p>","PeriodicalId":18214,"journal":{"name":"Medical Journal of Australia","volume":"223 4","pages":"180-184"},"PeriodicalIF":8.5000,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.5694/mja2.70012","citationCount":"0","resultStr":"{\"title\":\"Lung cancer biobanking in Australia: challenges and future directions\",\"authors\":\"Sarah Yeo, Stephen Q Wong, Farzaneh Atashrazm, Andreas Behren, Anthony T Papenfuss, Natalia Vukelic, Lisa Briggs, Ashleigh R Poh, Daniel Steinfort, Natasha Smallwood, Kate Sutherland, Vivek Naranbhai, Sagun Parakh, Tracy Leong\",\"doi\":\"10.5694/mja2.70012\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Lung cancer is the leading cause of cancer-related morbidity and mortality worldwide.<span><sup>1</sup></span> It is the fifth most common cancer diagnosed in Australia, but accounts for almost 20% of all cancer-related deaths, which is more than breast, prostate and ovarian cancer combined. Global advances in lung cancer management have been driven by early diagnosis, such as lung cancer screening, improved treatment options (targeted therapy and immunotherapy) and improvements in survivorship care. Despite this progress, the five-year survival rate for lung cancer in Australia is 24%.<span><sup>2</sup></span> Reasons for this poor outlook include late presentation with most lung cancer patients presenting with metastatic disease at the time of diagnosis, as well as tumour-specific features including a lack of reliable biomarkers, tumour heterogeneity and drug resistance.<span><sup>3</sup></span></p><p>Lung cancer biobanks facilitate translational research aimed at improving lung cancer diagnosis, prognosis and treatment in several ways.<span><sup>4</sup></span> These repositories collect and store high quality biological samples, such as tissue and blood, as well as detailed clinical information from patients across various stages of disease. This enables researchers to identify and validate predictive and prognostic biomarkers, discover molecular signatures associated with tumour progression and treatment resistance, and develop novel therapies and strategies to overcome resistance.<span><sup>5</sup></span></p><p>This perspective article provides a background on cancer biobanks, outlines the challenges specific to lung cancer biobanks in the Australian context, and discusses future directions.</p><p>Biobanks are defined by the Organisation for Economic Co-operation and Development as “a structured resource that can be used for the purpose of genetic research and which include: (a) human biological materials and/or information generated from the analysis of the same; and (b) extensive associated information”.<span><sup>6</sup></span> Cancer-focused biobanks are invaluable collections of biological specimens accompanied by matched health and demographic data. The International Agency for Research on Cancer states that biobanks underpin three rapidly expanding research fields aimed at developing effective strategies to prevent, diagnose and treat cancer: molecular and genetic epidemiology to assess the genetic and environmental bases of cancer; molecular pathology to develop molecular-based classifications and further phenotyping of different cancers; and pharmacogenomics/pharmaco–proteomics to understand the correlation between a patient's genotype/phenotype and their response to drug treatment.<span><sup>7</sup></span></p><p>With the assistance of a medical librarian, a search of Ovid MEDLINE(R) ALL 1946 to 4 April 2025 was conducted using a combination of MeSH headings and keywords containing “lung cancer” and “biobank” (search strategy provided in Supporting Information). There were 488 abstracts identified and screened, resulting in 379 relevant records. Of these, most (316) referred to research conducted using the UK Biobank, underscoring the importance of the UK Biobank in research and clinical contexts. Other cited biobanks included FinnGen (Finland) and China Kadoorie Biobank (China). Very few lung cancer-specific biobanks were identified, as summarised in Box 1.</p><p>Of the lung cancer biobanks described in Box 1, the only biobank currently collecting specimens, as well as being open for researchers’ applications is the Lung Biobank in Heidelberg, which has been operating for over 20 years with 16 000 patient specimens (with most specimens collected from people with lung cancer). Other lung cancer biobanks, such as the Shanghai Chest Hospital Lung Cancer Biobank, the Lung Cancer Biobank Nice and the European Early Lung Cancer Biobank, are no longer collecting specimens, and there is no clear online application pathway for researchers to apply to conduct research on collected specimens. Of these lung cancer biobanks, most lung cancer specimens are from surgical resections, which is concerning as most people with lung cancer have metastatic, unresectable disease, therefore the research produced from resected specimens may not be as relevant.</p><p>Australia is home to several well established pan-cancer biobanks as well as tumour-specific biobanks, but lung cancer biobanking in Australia is in its infancy. An example of an Australian cancer-agnostic biobank is the Victorian Cancer Biobank — which holds over 460 000 biospecimens — and provides access to samples collected in Victoria for approved research projects. The Victorian Cancer Biobank includes lung cancer specimens and as of April 2025, its catalogue listed lung cancer resection specimens from more than 50 donors and four metastatic lymph node specimens from two donors with advanced lung cancer.<span><sup>15</sup></span> There are also Australian cancer-specific biobanks, such as the Melanoma Institute Australia Biospecimen Bank, the Australian Breast Cancer Tissue Bank, and Brain Cancer Biobanking Australia. In addition, the new TRACKER (Tissue Repository of Airway Cancers for Knowledge Expansion of Resistance) lung cancer biobank is a consumer-partnered initiative focused on lung cancer.<span><sup>16</sup></span> TRACKER stores longitudinal biospecimens (including tumour tissue, peripheral blood and bronchoalveolar lavage fluid [BALF]) at diagnosis, during therapy and at disease progression.</p><p>Traditionally, lung cancer tissue for biobanking has been acquired through surgical resection of early-stage tumours, as this method provides large samples suitable for analysis. However, surgical biopsies are not representative of tumours in most individuals diagnosed with lung cancer, as most patients present with metastatic disease, which is inoperable.<span><sup>17</sup></span> Tissue acquisition from metastatic sites is often complex due to anatomical inaccessibility or patient-related factors and, as such, staging metastatic lung cancer can be challenging.<span><sup>18</sup></span> An example of a challenging metastatic site is the brain, which is difficult to obtain samples from without resection and usually carries high peri-operative risk. Similarly, liver and adrenal biopsies pose risks such as bleeding or bile leakage due to proximity to vascular structures, whereas bone biopsies are often painful and may not yield sufficient tissue for diagnosis.</p><p>Often the most practical methods for obtaining tissue for both diagnostic and biobanking purposes are minimally invasive bronchoscopic techniques such as linear endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for accessible nodal disease, and computed tomography-guided lung biopsies for direct sampling of lung lesions. Cytological specimens obtained from linear EBUS-TBNA procedures have been shown to provide adequate DNA yields for molecular analyses, including targeted and whole exome sequencing.<span><sup>19</sup></span> It is well established that the tumour microenvironment varies depending on anatomical site of disease.<span><sup>20</sup></span> Therefore, to facilitate the study of heterogenous responses to treatment, a biobank should include a range of anatomical samples.</p><p>Longitudinal sampling is crucial in lung cancer research due to the dynamic nature of biomarkers (eg, programmed death ligand-1; PD-L1), which vary both spatially (depending on the biopsy site) and temporally (changing throughout treatment). As immunotherapy efficacy is closely linked to PD-L1 expression levels, understanding resistance mechanisms necessitates repeated tissue sampling across different treatment phases. Minimally invasive procedures, such as EBUS-TBNA, allow for longitudinal sampling and can provide invaluable insights into tumour evolution, resistance mechanisms and patient-specific responses to therapies.<span><sup>8</sup></span></p><p>A key challenge with longitudinal sampling is the ethical and clinical concern of subjecting patients to repeated procedures purely for research purposes, which may increase patient risk and compromise ethical standards. When tissue is required for multiple purposes, including: (i) diagnosis; (ii) molecular analysis to guide treatment decisions; (iii) biobanking for future research; and (iv) eligibility for clinical trial enrolment, a single sample may not be sufficient to meet all these demands. Engaging with organisations that can facilitate access to archived tissue samples, or through participation in national networks, such as Lung Foundation Australia, the Thoracic Oncology Group Australasia, the Thoracic Society of Australia and New Zealand, and the Australian Registry and Biobank of Thoracic Cancers, allows for research collaboration, which may improve analysis methods so more can be done with less tissue.</p><p>Blood-based liquid biopsies offer a less invasive alternative for tracking circulating tumour DNA throughout the course of treatment, enabling monitoring of genomic alterations associated with therapy resistance.<span><sup>21</sup></span> Measuring circulating tumour DNA to assess tumour response is particularly valuable in lung cancer, where repeat tissue biopsies are often impractical. This approach allows for more refined prognostic assessments, tailored surveillance intervals and informed adjustments to therapy. Biobanks that collect a variety of lung cancer biospecimens longitudinally will be critical for translational research, helping to drive the development of personalised treatment strategies based on dynamic molecular profiling.</p><p>Translational research using biobanked lung cancer specimens encompasses a range of analytical approaches. These include genomic analysis (eg, identifying mutations such as in epidermal growth factor receptor [<i>EGFR</i>]), transcriptomic profiling (eg, assessing PD-L1 expression, which can correlate with immunotherapy response), and microbiome studies (eg, understanding how gut bacteria influence treatment outcomes). When these layers of data are combined, the approach is referred to as multi-omics, enabling comprehensive molecular profiling that supports the development of personalised treatment strategies tailored to the evolving nature of an individual's disease.</p><p>Integrating multi-omic data provides deeper insights into resistance mechanisms. This strategy can identify predictive biomarkers for systemic therapies as well as potential applications in surgical and radiotherapy interventions in future studies.</p><p>Internationally, efforts in achieving proportional ethnic diversity in biobanks have been driven by legislation, such as: (i) setting recruitment guidelines from the outset to ensure diversity and developing culturally competent guidelines for researchers; (ii) establishing ethnic diversity recruitment subgroups to broaden participation; and (iii) creating culturally informed research frameworks. In contrast, Australia lacks a legislative framework to guide the inclusion of Indigenous peoples and other ethnically diverse populations in biobanks or biomedical research.<span><sup>22</sup></span> Additional barriers for these priority populations, particularly Indigenous communities, include concerns surrounding the collection, storage and use of biological specimens, as well as uncertainties related to data sharing and ownership rights. Research involving Indigenous Australians must adapt study protocols to respect cultural values, address community priorities, ensure meaningful community consultation and include Indigenous researchers.<span><sup>23</sup></span></p><p>To enhance the relevance and impact of biobanks in health and medical research, it is vital to engage with patients, caregivers and consumer advocates. The stakeholder insights and feedback help shape study design, while participant information and consent processes ensure that research is patient-centred and reflective of real-world needs. Their involvement also strengthens advocacy efforts and recruitment strategies, fostering broader community trust and participation in research initiatives. By prioritising consumer engagement, we can build a research environment that authentically reflects the experiences and priorities of those it seeks to benefit.</p><p>Despite increasing efforts to support inclusive participation, significant gaps remain. There is a lack of diversity among consumers involved in research, echoing similar challenges seen in the composition of biobanked specimens. Priority populations — including populations with lower levels of health literacy, education and socio-economic status — continue to be under-represented.<span><sup>24</sup></span> This disparity persists despite the existence of national frameworks such as the National Framework for Consumer Involvement in Cancer Control.<span><sup>25</sup></span></p><p>The translational potential of biobanks depends on access to researchers who can effectively use these biospecimens for high quality analyses and publication in peer-reviewed journals, with the goal to improve outcomes of people with lung cancer (Box 2).</p><p>Despite considerable advances in lung cancer management, significant challenges remain in improving patient outcomes. High quality, long term, consumer-partnered lung cancer biobanks are critical to advancing the necessary translational research.</p><p>The development of large, clinically annotated, multi-omic datasets from lung cancer patients will provide essential insights into predictive and prognostic biomarkers and identify novel therapeutic targets to overcome resistance and improve treatment responses. Enhancing patient selection for clinical trials and identifying new agents to target resistance mechanisms may enable more personalised therapies. This will facilitate the design of synergistic combination strategies for treatment-refractory patients.</p><p>Reducing treatment resistance will ultimately lead to better clinical outcomes, improved survival and enhanced quality of life for patients with lung cancer. Lung cancer biobanking is a crucial step in building the infrastructure needed to enable access to biospecimens and associated multi-omic and clinical data for researchers both nationally and internationally. This will increase research efficiency, reduce costs and, most importantly, foster greater collaboration, all with the goal of improving the lives and outcomes of people affected by cancer.</p><p>Open access publishing facilitated by The University of Melbourne, as part of the Wiley - The University of Melbourne agreement via the Council of Australian University Librarians.</p><p>No relevant disclosures.</p><p>Not commissioned; externally peer reviewed.</p><p>Yeo S: Investigation, methodology, visualization, writing - original draft, writing - review and editing. Wong SQ: Writing - review and editing. Atashrazm F: Resources, writing - review and editing. Behren A: Conceptualization, writing - review and editing. Papenfuss AT: Writing - review and editing. Vukelic N: Project administration, resources, writing - original draft, writing - review and editing. Briggs L: Conceptualization, writing - review and editing. Poh AR: Writing - review and editing. Steinfort D: Supervision, writing - review and editing. Smallwood N: Supervision, writing - review and editing. Sutherland K: Supervision, writing - review and editing. Naranbhai V: Supervision, writing - review and editing. Parakh S: Conceptualization, supervision, writing - original draft, writing - review and editing. Leong T: Conceptualization, supervision, writing - original draft, writing - review and editing.</p>\",\"PeriodicalId\":18214,\"journal\":{\"name\":\"Medical Journal of Australia\",\"volume\":\"223 4\",\"pages\":\"180-184\"},\"PeriodicalIF\":8.5000,\"publicationDate\":\"2025-07-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.5694/mja2.70012\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Medical Journal of Australia\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.5694/mja2.70012\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, GENERAL & INTERNAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Medical Journal of Australia","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.5694/mja2.70012","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
引用次数: 0
摘要
肺癌是全球癌症相关发病率和死亡率的主要原因它是澳大利亚第五大最常见的癌症,但占所有癌症相关死亡人数的近20%,超过了乳腺癌、前列腺癌和卵巢癌的总和。早期诊断(如肺癌筛查)、改进的治疗选择(靶向治疗和免疫治疗)以及改善的生存护理推动了肺癌管理的全球进展。尽管取得了这一进展,但澳大利亚肺癌的五年生存率为24%前景不佳的原因包括大多数肺癌患者在诊断时出现转移性疾病,以及肿瘤特异性特征,包括缺乏可靠的生物标志物,肿瘤异质性和耐药性。肺癌生物库从多个方面促进了旨在改善肺癌诊断、预后和治疗的转化研究这些储存库收集和储存高质量的生物样本,如组织和血液,以及来自不同疾病阶段患者的详细临床信息。这使研究人员能够识别和验证预测和预后的生物标志物,发现与肿瘤进展和治疗耐药性相关的分子特征,并开发新的治疗方法和策略来克服耐药性。这篇前瞻性文章提供了癌症生物库的背景,概述了澳大利亚肺癌生物库特有的挑战,并讨论了未来的发展方向。经济合作与发展组织将生物银行定义为“可用于遗传研究目的的结构化资源,其中包括:(a)人类生物材料和/或从其分析中产生的信息;(b)广泛的有关资料”以癌症为重点的生物库是宝贵的生物标本集合,并附有匹配的健康和人口统计数据。国际癌症研究机构(International Agency for Research on Cancer)指出,生物库支撑着三个快速发展的研究领域,旨在制定预防、诊断和治疗癌症的有效策略:分子和遗传流行病学,以评估癌症的遗传和环境基础;分子病理学发展基于分子的分类和不同癌症的进一步表型;以及药物基因组学/药物蛋白质组学,以了解患者的基因型/表型与其对药物治疗的反应之间的关系。在医学图书管理员的协助下,使用包含“肺癌”和“生物银行”的MeSH标题和关键词组合对Ovid MEDLINE(R) ALL 1946至2025年4月4日进行了搜索(搜索策略见辅助信息)。筛选出488篇摘要,得到379条相关记录。其中,大多数(316)涉及使用UK Biobank进行的研究,强调了UK Biobank在研究和临床环境中的重要性。其他被引用的生物银行包括FinnGen(芬兰)和中国嘉道理生物银行(中国)。很少有肺癌特异性生物库被确定,如框1所示。在方框1中描述的肺癌生物库中,目前唯一收集标本并向研究人员开放的生物库是海德堡的肺生物库,该生物库已经运营了20多年,拥有16000例患者标本(大多数标本来自肺癌患者)。其他肺癌生物库,如上海胸科医院肺癌生物库、尼斯肺癌生物库和欧洲早期肺癌生物库等,已不再采集标本,研究人员也没有明确的在线申请途径,可以申请对采集的标本进行研究。在这些肺癌生物库中,大多数肺癌标本来自手术切除,这是令人担忧的,因为大多数肺癌患者都有转移性,不可切除的疾病,因此从切除标本中产生的研究可能不那么相关。澳大利亚有几个建立良好的泛癌症生物银行和肿瘤特异性生物银行,但澳大利亚的肺癌生物银行还处于起步阶段。澳大利亚癌症不可知论生物银行的一个例子是维多利亚癌症生物银行,它拥有超过46万个生物标本,并为批准的研究项目提供在维多利亚州收集的样本。维多利亚癌症生物银行包括肺癌标本,截至2025年4月,其目录列出了来自50多个捐赠者的肺癌切除标本和来自两个晚期肺癌捐赠者的四个转移性淋巴结标本澳大利亚也有专门针对癌症的生物银行,如澳大利亚黑色素瘤研究所生物标本银行、澳大利亚乳腺癌组织银行和澳大利亚脑癌生物银行。 当这些数据层结合在一起时,这种方法被称为多组学,能够实现全面的分子谱分析,支持针对个体疾病不断变化的本质制定个性化治疗策略。整合多组学数据可以更深入地了解抗性机制。这一策略可以识别系统性治疗的预测性生物标志物,以及在未来研究中外科和放疗干预的潜在应用。在国际上,实现生物库中种族比例多样性的努力一直受到立法的推动,例如:(i)从一开始就制定招聘准则,以确保多样性,并为研究人员制定符合文化的指导方针;(ii)设立种族多元化的招聘小组,以扩大参与;(三)创建具有文化背景的研究框架。相比之下,澳大利亚缺乏一个立法框架来指导将土著人民和其他族裔多样化的人口纳入生物银行或生物医学研究这些重点人群,特别是土著社区面临的其他障碍包括对生物标本的收集、储存和使用的担忧,以及与数据共享和所有权有关的不确定性。涉及土著澳大利亚人的研究必须调整研究方案,以尊重文化价值观,解决社区优先事项,确保有意义的社区咨询,并包括土著研究人员。23 .为了加强生物银行在卫生和医学研究中的相关性和影响,与患者、护理人员和消费者权益倡导者进行接触至关重要。利益相关者的见解和反馈有助于塑造研究设计,而参与者信息和同意过程确保研究以患者为中心,并反映现实世界的需求。他们的参与还加强了宣传工作和招聘战略,促进了更广泛的社区信任和对研究活动的参与。通过优先考虑消费者的参与,我们可以建立一个研究环境,真实地反映那些它寻求受益的人的经验和优先事项。尽管加大了支持包容性参与的努力,但仍存在巨大差距。参与研究的消费者缺乏多样性,这与生物样本组成方面的类似挑战相呼应。24 .优先人口——包括卫生知识普及程度、教育水平和社会经济地位较低的人口——的代表性仍然不足尽管存在诸如《消费者参与癌症控制国家框架》之类的国家框架,但这种差异仍然存在。25生物库的转化潜力取决于能够有效利用这些生物标本进行高质量分析并在同行评议期刊上发表的研究人员,其目标是改善肺癌患者的预后(方框2)。尽管肺癌治疗取得了相当大的进步,但在改善患者预后方面仍存在重大挑战。高质量、长期、消费者合作的肺癌生物库对于推进必要的转化研究至关重要。来自肺癌患者的大型、临床注释、多组学数据集的开发将为预测和预后生物标志物提供重要见解,并确定新的治疗靶点,以克服耐药性和改善治疗反应。加强临床试验的患者选择和确定针对耐药机制的新药可能会使治疗更加个性化。这将有助于为难治性患者设计协同联合策略。减少治疗耐药性将最终带来更好的临床结果,改善肺癌患者的生存和提高生活质量。肺癌生物银行是建立基础设施的关键一步,使国内和国际的研究人员能够获得生物标本和相关的多组学和临床数据。这将提高研究效率,降低成本,最重要的是,促进更大的合作,所有这些都是为了改善癌症患者的生活和结果。开放获取出版由墨尔本大学促进,作为Wiley -墨尔本大学协议的一部分,通过澳大利亚大学图书馆员理事会。无相关披露。不是委托;外部同行评审。Yeo S:调查,方法论,可视化,写作-原稿,写作-审查和编辑。王思平:写作-审查和编辑。Atashrazm F:资源,写作-审查和编辑。概念化,写作-评论和编辑。论文:写作-审查和编辑。Vukelic N:项目管理,资源,写作-原稿,写作-审查和编辑。 概念化,写作-评论和编辑。Poh AR:写作-审查和编辑。监督、写作、审查和编辑。监督、写作、审查和编辑。Sutherland K:监督,写作-评论和编辑。Naranbhai V:监督,写作-审查和编辑。构思,监督,写作-原稿,写作-审查和编辑。梁涛:构思、监督、撰写-原稿、撰写-审稿、编辑。
Lung cancer biobanking in Australia: challenges and future directions
Lung cancer is the leading cause of cancer-related morbidity and mortality worldwide.1 It is the fifth most common cancer diagnosed in Australia, but accounts for almost 20% of all cancer-related deaths, which is more than breast, prostate and ovarian cancer combined. Global advances in lung cancer management have been driven by early diagnosis, such as lung cancer screening, improved treatment options (targeted therapy and immunotherapy) and improvements in survivorship care. Despite this progress, the five-year survival rate for lung cancer in Australia is 24%.2 Reasons for this poor outlook include late presentation with most lung cancer patients presenting with metastatic disease at the time of diagnosis, as well as tumour-specific features including a lack of reliable biomarkers, tumour heterogeneity and drug resistance.3
Lung cancer biobanks facilitate translational research aimed at improving lung cancer diagnosis, prognosis and treatment in several ways.4 These repositories collect and store high quality biological samples, such as tissue and blood, as well as detailed clinical information from patients across various stages of disease. This enables researchers to identify and validate predictive and prognostic biomarkers, discover molecular signatures associated with tumour progression and treatment resistance, and develop novel therapies and strategies to overcome resistance.5
This perspective article provides a background on cancer biobanks, outlines the challenges specific to lung cancer biobanks in the Australian context, and discusses future directions.
Biobanks are defined by the Organisation for Economic Co-operation and Development as “a structured resource that can be used for the purpose of genetic research and which include: (a) human biological materials and/or information generated from the analysis of the same; and (b) extensive associated information”.6 Cancer-focused biobanks are invaluable collections of biological specimens accompanied by matched health and demographic data. The International Agency for Research on Cancer states that biobanks underpin three rapidly expanding research fields aimed at developing effective strategies to prevent, diagnose and treat cancer: molecular and genetic epidemiology to assess the genetic and environmental bases of cancer; molecular pathology to develop molecular-based classifications and further phenotyping of different cancers; and pharmacogenomics/pharmaco–proteomics to understand the correlation between a patient's genotype/phenotype and their response to drug treatment.7
With the assistance of a medical librarian, a search of Ovid MEDLINE(R) ALL 1946 to 4 April 2025 was conducted using a combination of MeSH headings and keywords containing “lung cancer” and “biobank” (search strategy provided in Supporting Information). There were 488 abstracts identified and screened, resulting in 379 relevant records. Of these, most (316) referred to research conducted using the UK Biobank, underscoring the importance of the UK Biobank in research and clinical contexts. Other cited biobanks included FinnGen (Finland) and China Kadoorie Biobank (China). Very few lung cancer-specific biobanks were identified, as summarised in Box 1.
Of the lung cancer biobanks described in Box 1, the only biobank currently collecting specimens, as well as being open for researchers’ applications is the Lung Biobank in Heidelberg, which has been operating for over 20 years with 16 000 patient specimens (with most specimens collected from people with lung cancer). Other lung cancer biobanks, such as the Shanghai Chest Hospital Lung Cancer Biobank, the Lung Cancer Biobank Nice and the European Early Lung Cancer Biobank, are no longer collecting specimens, and there is no clear online application pathway for researchers to apply to conduct research on collected specimens. Of these lung cancer biobanks, most lung cancer specimens are from surgical resections, which is concerning as most people with lung cancer have metastatic, unresectable disease, therefore the research produced from resected specimens may not be as relevant.
Australia is home to several well established pan-cancer biobanks as well as tumour-specific biobanks, but lung cancer biobanking in Australia is in its infancy. An example of an Australian cancer-agnostic biobank is the Victorian Cancer Biobank — which holds over 460 000 biospecimens — and provides access to samples collected in Victoria for approved research projects. The Victorian Cancer Biobank includes lung cancer specimens and as of April 2025, its catalogue listed lung cancer resection specimens from more than 50 donors and four metastatic lymph node specimens from two donors with advanced lung cancer.15 There are also Australian cancer-specific biobanks, such as the Melanoma Institute Australia Biospecimen Bank, the Australian Breast Cancer Tissue Bank, and Brain Cancer Biobanking Australia. In addition, the new TRACKER (Tissue Repository of Airway Cancers for Knowledge Expansion of Resistance) lung cancer biobank is a consumer-partnered initiative focused on lung cancer.16 TRACKER stores longitudinal biospecimens (including tumour tissue, peripheral blood and bronchoalveolar lavage fluid [BALF]) at diagnosis, during therapy and at disease progression.
Traditionally, lung cancer tissue for biobanking has been acquired through surgical resection of early-stage tumours, as this method provides large samples suitable for analysis. However, surgical biopsies are not representative of tumours in most individuals diagnosed with lung cancer, as most patients present with metastatic disease, which is inoperable.17 Tissue acquisition from metastatic sites is often complex due to anatomical inaccessibility or patient-related factors and, as such, staging metastatic lung cancer can be challenging.18 An example of a challenging metastatic site is the brain, which is difficult to obtain samples from without resection and usually carries high peri-operative risk. Similarly, liver and adrenal biopsies pose risks such as bleeding or bile leakage due to proximity to vascular structures, whereas bone biopsies are often painful and may not yield sufficient tissue for diagnosis.
Often the most practical methods for obtaining tissue for both diagnostic and biobanking purposes are minimally invasive bronchoscopic techniques such as linear endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for accessible nodal disease, and computed tomography-guided lung biopsies for direct sampling of lung lesions. Cytological specimens obtained from linear EBUS-TBNA procedures have been shown to provide adequate DNA yields for molecular analyses, including targeted and whole exome sequencing.19 It is well established that the tumour microenvironment varies depending on anatomical site of disease.20 Therefore, to facilitate the study of heterogenous responses to treatment, a biobank should include a range of anatomical samples.
Longitudinal sampling is crucial in lung cancer research due to the dynamic nature of biomarkers (eg, programmed death ligand-1; PD-L1), which vary both spatially (depending on the biopsy site) and temporally (changing throughout treatment). As immunotherapy efficacy is closely linked to PD-L1 expression levels, understanding resistance mechanisms necessitates repeated tissue sampling across different treatment phases. Minimally invasive procedures, such as EBUS-TBNA, allow for longitudinal sampling and can provide invaluable insights into tumour evolution, resistance mechanisms and patient-specific responses to therapies.8
A key challenge with longitudinal sampling is the ethical and clinical concern of subjecting patients to repeated procedures purely for research purposes, which may increase patient risk and compromise ethical standards. When tissue is required for multiple purposes, including: (i) diagnosis; (ii) molecular analysis to guide treatment decisions; (iii) biobanking for future research; and (iv) eligibility for clinical trial enrolment, a single sample may not be sufficient to meet all these demands. Engaging with organisations that can facilitate access to archived tissue samples, or through participation in national networks, such as Lung Foundation Australia, the Thoracic Oncology Group Australasia, the Thoracic Society of Australia and New Zealand, and the Australian Registry and Biobank of Thoracic Cancers, allows for research collaboration, which may improve analysis methods so more can be done with less tissue.
Blood-based liquid biopsies offer a less invasive alternative for tracking circulating tumour DNA throughout the course of treatment, enabling monitoring of genomic alterations associated with therapy resistance.21 Measuring circulating tumour DNA to assess tumour response is particularly valuable in lung cancer, where repeat tissue biopsies are often impractical. This approach allows for more refined prognostic assessments, tailored surveillance intervals and informed adjustments to therapy. Biobanks that collect a variety of lung cancer biospecimens longitudinally will be critical for translational research, helping to drive the development of personalised treatment strategies based on dynamic molecular profiling.
Translational research using biobanked lung cancer specimens encompasses a range of analytical approaches. These include genomic analysis (eg, identifying mutations such as in epidermal growth factor receptor [EGFR]), transcriptomic profiling (eg, assessing PD-L1 expression, which can correlate with immunotherapy response), and microbiome studies (eg, understanding how gut bacteria influence treatment outcomes). When these layers of data are combined, the approach is referred to as multi-omics, enabling comprehensive molecular profiling that supports the development of personalised treatment strategies tailored to the evolving nature of an individual's disease.
Integrating multi-omic data provides deeper insights into resistance mechanisms. This strategy can identify predictive biomarkers for systemic therapies as well as potential applications in surgical and radiotherapy interventions in future studies.
Internationally, efforts in achieving proportional ethnic diversity in biobanks have been driven by legislation, such as: (i) setting recruitment guidelines from the outset to ensure diversity and developing culturally competent guidelines for researchers; (ii) establishing ethnic diversity recruitment subgroups to broaden participation; and (iii) creating culturally informed research frameworks. In contrast, Australia lacks a legislative framework to guide the inclusion of Indigenous peoples and other ethnically diverse populations in biobanks or biomedical research.22 Additional barriers for these priority populations, particularly Indigenous communities, include concerns surrounding the collection, storage and use of biological specimens, as well as uncertainties related to data sharing and ownership rights. Research involving Indigenous Australians must adapt study protocols to respect cultural values, address community priorities, ensure meaningful community consultation and include Indigenous researchers.23
To enhance the relevance and impact of biobanks in health and medical research, it is vital to engage with patients, caregivers and consumer advocates. The stakeholder insights and feedback help shape study design, while participant information and consent processes ensure that research is patient-centred and reflective of real-world needs. Their involvement also strengthens advocacy efforts and recruitment strategies, fostering broader community trust and participation in research initiatives. By prioritising consumer engagement, we can build a research environment that authentically reflects the experiences and priorities of those it seeks to benefit.
Despite increasing efforts to support inclusive participation, significant gaps remain. There is a lack of diversity among consumers involved in research, echoing similar challenges seen in the composition of biobanked specimens. Priority populations — including populations with lower levels of health literacy, education and socio-economic status — continue to be under-represented.24 This disparity persists despite the existence of national frameworks such as the National Framework for Consumer Involvement in Cancer Control.25
The translational potential of biobanks depends on access to researchers who can effectively use these biospecimens for high quality analyses and publication in peer-reviewed journals, with the goal to improve outcomes of people with lung cancer (Box 2).
Despite considerable advances in lung cancer management, significant challenges remain in improving patient outcomes. High quality, long term, consumer-partnered lung cancer biobanks are critical to advancing the necessary translational research.
The development of large, clinically annotated, multi-omic datasets from lung cancer patients will provide essential insights into predictive and prognostic biomarkers and identify novel therapeutic targets to overcome resistance and improve treatment responses. Enhancing patient selection for clinical trials and identifying new agents to target resistance mechanisms may enable more personalised therapies. This will facilitate the design of synergistic combination strategies for treatment-refractory patients.
Reducing treatment resistance will ultimately lead to better clinical outcomes, improved survival and enhanced quality of life for patients with lung cancer. Lung cancer biobanking is a crucial step in building the infrastructure needed to enable access to biospecimens and associated multi-omic and clinical data for researchers both nationally and internationally. This will increase research efficiency, reduce costs and, most importantly, foster greater collaboration, all with the goal of improving the lives and outcomes of people affected by cancer.
Open access publishing facilitated by The University of Melbourne, as part of the Wiley - The University of Melbourne agreement via the Council of Australian University Librarians.
No relevant disclosures.
Not commissioned; externally peer reviewed.
Yeo S: Investigation, methodology, visualization, writing - original draft, writing - review and editing. Wong SQ: Writing - review and editing. Atashrazm F: Resources, writing - review and editing. Behren A: Conceptualization, writing - review and editing. Papenfuss AT: Writing - review and editing. Vukelic N: Project administration, resources, writing - original draft, writing - review and editing. Briggs L: Conceptualization, writing - review and editing. Poh AR: Writing - review and editing. Steinfort D: Supervision, writing - review and editing. Smallwood N: Supervision, writing - review and editing. Sutherland K: Supervision, writing - review and editing. Naranbhai V: Supervision, writing - review and editing. Parakh S: Conceptualization, supervision, writing - original draft, writing - review and editing. Leong T: Conceptualization, supervision, writing - original draft, writing - review and editing.
期刊介绍:
The Medical Journal of Australia (MJA) stands as Australia's foremost general medical journal, leading the dissemination of high-quality research and commentary to shape health policy and influence medical practices within the country. Under the leadership of Professor Virginia Barbour, the expert editorial team at MJA is dedicated to providing authors with a constructive and collaborative peer-review and publication process. Established in 1914, the MJA has evolved into a modern journal that upholds its founding values, maintaining a commitment to supporting the medical profession by delivering high-quality and pertinent information essential to medical practice.