Clinical and translational discovery最新文献

{"title":"Precision treatment paradigm: Genomic features and therapeutic implications in mesenchymal-epithelial transition-amplified gastric cancer","authors":"Yiyi Yu,&nbsp;Zhening Zhang,&nbsp;Mengxuan Zhu,&nbsp;Yu Shan,&nbsp;Yan Wang,&nbsp;Li Wei,&nbsp;Xuan Huang,&nbsp;Debin Sun,&nbsp;Zhao Peng,&nbsp;Tianshu Liu","doi":"10.1002/ctd2.350","DOIUrl":"https://doi.org/10.1002/ctd2.350","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Despite advances in treatments for gastric cancer (GC), new targets are needed to enhance treatment, especially when mesenchymal-epithelial transition (<i>MET</i>) amplification is involved. Therefore, we investigated the genomic features of <i>MET</i>-amplified GC and efficacy of anti-<i>MET</i> therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Genomic features were investigated in 2284 patients (cohort 1) and 438 patients in the Cancer Genome Atlas (TCGA cohort). RNA data were obtained from TCGA for expression analysis. Clinical responses of 71 patients (cohort 2) were investigated. Survival rates were compared by Kaplan–Meier and log-rank tests.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In cohort 1, 95 (4.2%) exhibited <i>MET</i> amplifications. In TCGA cohort, 15 (3.4%) exhibited <i>MET</i> amplifications. The five top mutated genes were <i>TP53</i>, <i>CDH1</i>, <i>ARID1A</i>, <i>KMT2D</i> and <i>PIK3CA</i> in cohort 1 and <i>TTN</i>, <i>TP53</i>, <i>MUC16</i>, <i>LRP1B</i> and <i>SYNE1</i> in TCGA cohort. <i>TP53</i>, <i>PIK3CA</i>, <i>KRAS</i> and <i>GNAS</i> showed significant single nucleotide variants (SNVs) in cohort 1, and <i>TP53</i> SNVs were significant in TCGA cohort. Fifteen and 18 genes showed significant copy number variations (CNVs) between the <i>MET</i>- and non-<i>MET</i>-amplified groups in cohort 1 and TCGA cohort, respectively. The PI3K pathway was significantly activated in Chinese patients with <i>MET</i>-amplified GC (<i>p</i> = 0.002). TP53 expression is negatively associated with <i>MET</i> amplification. Real-world data obtained with cohort 2 revealed that anti-<i>MET</i> treatment significantly affected overall survival (OS) (<i>p</i> = 0.002), whereas CNVs did not affect progression-free or OS even when treatment lines were considered.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p><i>MET-</i>amplified GC has a distinctive mutation landscape. Our findings provide valuable information for clinicians who treat patients with <i>MET-</i>amplified GC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.350","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141968416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exporting nuclear export inhibitors from hematologic to solid tumour malignancies","authors":"Alexandra Chirino,&nbsp;Alyssa Maye,&nbsp;Justin Taylor","doi":"10.1002/ctd2.356","DOIUrl":"https://doi.org/10.1002/ctd2.356","url":null,"abstract":"<p>Exportin 1 (XPO1), formerly known as chromosomal region maintenance 1, belongs to the karyopherin family of proteins that are responsible for the import and export of macromolecules through the nuclear pore complex. XPO1 is the sole exporter of hundreds of cargoes including several RNA species and key proteins such as tumor suppressors and cell cycle proteins. Despite its essential and housekeeping function in normal cells, in their review, Lai et al note that upregulation of XPO1 is associated with a wide variety of cancers, including but not limited to colorectal cancer, osteosarcoma, lung cancer, gastric cancer, ovarian cancer, glioma, pancreatic cancer and oesophagal cancer.<span>¹</span> In non-cancer cells, XPO1 shuttles RNA and proteins from the nucleus to the cytoplasm while also regulating mitosis during interphase. After performing its export function, XPO1 returns to the nucleus to repeat the process, making it a vital part of sustaining normal cellular physiological functions (Figure 1). However, increased expression of XPO1 leads to increased export and imbalance of nucleo-cytoplasmic transport.</p><p>Though the exact mechanisms regulating the overexpression of XPO1 in solid cancers are not yet completely understood, chromosome 2p amplification accounts for this in a subset of hematologic neoplasms. Another means of dysregulation of XPO1 that is found in hematologic malignancies is the missense mutation <i>XPO1</i> E517K, which has been linked to facilitating the growth of malignant B cells in chronic lymphocytic leukaemia and Hodgkin lymphoma.<span>²</span> Clinical trials of XPO1 inhibitors in hematologic malignancies have shown response rates ranging from 26% to 45% in those with advanced multiple myeloma, and a 28% response rate in those with relapsed or refractory diffuse large B cell lymphoma.<span>^3-5</span> Due to this success, selinexor, the first-in-class XPO1 inhibitor has been Food and Drug Administration-approved for these two indications.</p><p>This leads to the big question—can targeting XPO1 be successful in solid tumours? According to Lai et al, while promising, it comes with considerable challenges. The first XPO1 inhibitors were natural products that irreversibly bound XPO1 and caused severe toxic side effects, leading to the discontinuation of their development as anticancer therapies. In response, small molecule XPO1 inhibitors were designed to be slowly reversible and are more tolerable in patients. Preclinical data suggests that selinexor is active in tumours with previous drug resistance in vitro and in vivo and induces apoptosis in many cancerous cell lines including but not limited to prostate, bladder, and renal cell carcinoma. While reducing the tumour is the main goal for these preclinical studies, there are questions of dose dependency for cancers like sarcomas, which may not be feasible for humans in clinical trials.<span>⁶</span> However, that is not to di","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.356","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141968288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacterial surface derived extracellular vesicles: A ground-breaking approach in cancer therapy","authors":"Asmit Das,&nbsp;Swarup Sonar,&nbsp;Ketki Kalele,&nbsp;Vetriselvan Subramaniyan","doi":"10.1002/ctd2.351","DOIUrl":"10.1002/ctd2.351","url":null,"abstract":"<p>Conventional cancer therapies are often limited by inherent and acquired drug resistance, non-specific toxicity, and suboptimal drug delivery. Bacterial extracellular vesicles (BEVs), including outer membrane vesicles and membrane vesicles, present a novel therapeutic strategy for cancer treatment. BEVs were found in both Gram-negative and Gram-positive bacteria. This article provides a classified investigation of the therapeutic potential of BEVs in cancer treatment. We discuss the molecular mechanisms underlying their observed anti-tumor effects, including the induction of apoptosis in cancer cells, suppression of angiogenesis within the tumor microenvironment, and stimulation of both innate and adaptive anti-tumor immune responses. Moreover, BEVs being biocompatible opens avenue for targeted drug delivery systems, potentially improving the therapeutic index of conventional chemotherapeutics. Challenges to clinical translation, such as BEV heterogeneity and potential immunogenicity, are addressed. We also explore future directions for research and development, comprehensively highlighting how BEVs transform the landscape of precision oncology and cancer treatment, eventually improving patient outcomes.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.351","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141797183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The crosstalk between N6-methyladenosine readers and neuroblastoma","authors":"Liping Chen,&nbsp;Jing He,&nbsp;Zhenjian Zhuo","doi":"10.1002/ctd2.344","DOIUrl":"10.1002/ctd2.344","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neuroblastoma (NB) is a heterogeneous pediatric solid tumour strongly influenced by epigenetic modifications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This review explores the role of N6-methyladenosine (m6A) modifications and their readers in NB progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Dysregulation of m6A readers, including YTHDF1/2, YTHDC1, IGF2BP1/2/3, HNRNPA2B1 and HNRNPC, has been associated with susceptibility and progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Understanding the crosstalk between m6A readers and NB could offer new insights into diagnosis, prognosis, and treatment strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.344","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141810680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plant-derived exosomes: A Green Nanomedicine for Cancer","authors":"Swarup Sonar,&nbsp;Krishnan Anand","doi":"10.1002/ctd2.333","DOIUrl":"10.1002/ctd2.333","url":null,"abstract":"<p>Exosomes are signalling molecules related to cell-to-cell communication. Based on sources (plants, stem cells, and immune cells derived exosomes) it offers promising therapeutic activity against cancer. Plant-derived exosomes (PDEs) are natural extracellular vesicles (EVs) that are potent to provide organic precision nanomedicine to cancer therapeutics including targeted drug delivery. PDEs are gaining attention due to their safety and efficacy. There are plenty of different sources of PDEs in nature. This article explores various plants such as carrots, ginger, lemons, cabbages, blueberries, oranges, tomatoes, grapefruits, and tea leaves, which provide exosomes with distinct therapeutic properties, including anti-inflammatory, antioxidant, and anticancer activities. PDEs exhibit significant potential in drug delivery. Ongoing research and clinical trials predict that PDEs will become effective, and affordable solutions for cancer treatment.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.333","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141818336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Milk exosomes: Harnessing nature's duality for cancer therapy","authors":"Asmit Das,&nbsp;Swarup Sonar,&nbsp;Ketki Kalele,&nbsp;Vetriselvan Subramaniyan","doi":"10.1002/ctd2.349","DOIUrl":"https://doi.org/10.1002/ctd2.349","url":null,"abstract":"<p>Milk exosomes, extracellular nanovesicles that are naturally present in milk, have gained significant attention in cancer research for their potential to revolutionize cancer treatment strategies. They possess a specific set of characteristics that make them promising nanoscale vehicles for targeted drug delivery systems. Their inherent biocompatibility, coupled with their ability to effectively encapsulate and transport therapeutic agents directly into tumor cells, suggests the possibility of developing novel cancer therapies, potentially minimizing side effects associated with conventional therapies. However, recent studies have shown that milk exosomes have a dual nature, which is not entirely positive. Although they show potential in delivering anticancer therapeutics, evidence suggests they may also, under certain conditions, contribute to cancer progression. This paradoxical nature necessitates a better understanding of how they interact and work in different stages of cancer. Further investigation is crucial to understand the factors influencing their behaviour and to develop strategies that can maximize their therapeutic prospects while mitigating potential risks associated with their use in cancer treatment.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.349","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141732551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel insights into the pathological features of COPD: Focus on oxidative stress and mitophagy","authors":"Jiameng Gao,&nbsp;Yao Shen,&nbsp;Zhihong Chen","doi":"10.1002/ctd2.343","DOIUrl":"https://doi.org/10.1002/ctd2.343","url":null,"abstract":"<p>Chronic airway obstructive pulmonary disease (COPD) is a preventable and curable disease characterised by persistent airflow limitation. It is characterised by chronic bronchitis and/or emphysema, and its aetiology is related to various factors such as smoking and infectious factors, and so forth. The pathogenesis is complex and prone to frequent exacerbations, and the prognosis of acute exacerbations of COPD is often poor. As a crucial component of the innate immune system, lung macrophages significantly influence the onset and progression of COPD. When macrophage mitochondria become dysfunctional, many macrophage functions (e.g., phagocytosis, cytokine secretion, chemotaxis, etc.) change. The aim of this paper is to describe the three major pathological features of COPD (oxidative stress imbalance, macrophage polarisation and mitochondrial membrane potential [MMP] production and mitochondrial autophagy), to describe in detail the mechanism of mitochondrial autophagy pathway and its association with oxidative stress and macrophage polarisation and to emphasise the role of macrophage mitochondrial reactive oxygen species (mROS) in COPD, with the aim of providing ideas and directions for subsequent studies.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.343","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141732550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tracking down metabolic vulnerabilities in CDK12-mutant prostate cancer","authors":"Wei-Ling Tu,&nbsp;Mu-En Wang,&nbsp;Ming Chen","doi":"10.1002/ctd2.345","DOIUrl":"https://doi.org/10.1002/ctd2.345","url":null,"abstract":"<p><i>CDK12</i> is among the most frequently mutated cyclin-dependent kinases (CDKs) in various cancers, including prostate, ovarian, breast, esophageal, bladder, and colon cancers.<span>¹</span> Specifically, biallelic aberrations of <i>CDK12</i> occur in 3%–7% of metastatic castration-resistant prostate cancer (mCRPC) cases and correlate with poor prognosis.<span>¹</span> One of the most well-studied functions of CDK12 is its orchestration of transcription initiation and elongation through cyclin K-dependent Ser2 phosphorylation of RNA polymerase II,<span>²</span> and therefore CDK12 is important in regulating the expression of long genes or genes with high exon numbers, especially DNA damage response (DDR)-related genes such as <i>BRCA1</i>, <i>ATR</i>, <i>FANCI</i>, and <i>FANCD21</i>.<span>³</span> As a result, <i>CDK12</i>-deficient cancers are commonly characterized by focal tandem duplications (FTDs) and various features of genome instability.<span>^{4, 5}</span> Because FTDs often generate a large amount of neoantigens, it has been suggested that <i>CDK12</i>-deficient tumours may be more sensitive to immunotherapy.<span>⁵</span> However, studies of immune checkpoint blockade therapy have shown only limited effects in mCRPC patients harbouring <i>CDK12</i> mutations.<span>⁶</span> Likewise, despite the observed sensitization of <i>CDK12</i>-deficient ovarian cancer cells to PARP inhibitors (PARPi) due to impaired DDR functionality,<span>⁷</span> clinical trials of PARPi have produced unsatisfactory results in prostate cancer patients with <i>CDK12</i> mutations.<span>⁶</span> Therefore, there is an urgent need to identify exploitable vulnerabilities in <i>CDK12</i>-deficient prostate cancer.</p><p>In a recent study, Zhang et al. investigated the impact of <i>CDK12</i> deficiency on cell metabolism and tumour progression in prostate cancer.<span>⁸</span> By analyzing public datasets, they confirmed an association between <i>CDK12</i> deficiency and poor prognosis in mCRPC, while noting higher levels of <i>CDK12</i> mutations in Chinese patients (15.4%–27.2%) than in the global populations (4.7%). To further delineate how <i>CDK12</i> deficiency promotes mCRPC, they generated <i>CDK12</i>-knockout prostate cancer cell lines using CRISPR-Cas9 technology and conducted metabolomic and transcriptomic analyses. The resulting data showed that <i>CDK12</i> deficiency reprogrammed energy metabolisms in prostate cancer cells; specifically, <i>CDK12</i> knockout cells exhibited higher levels of metabolites related to glycolysis, glutaminolysis, and the tricarboxylic acid cycle, but lower levels of metabolites related to β-oxidation. Further, the associated RNA-seq data showed enrichment of mitochondrial electron transport chain (ETC) and oxidative phosphorylation-related pathways in <i>CDK12</i>-deficient prostate cancers, suggesting that <i>CD","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.345","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141732552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical signature of exosomal tetraspanin proteins in cancer","authors":"Asmit Das,&nbsp;Priyanka Saha,&nbsp;Ketki Kalele,&nbsp;Swarup Sonar","doi":"10.1002/ctd2.341","DOIUrl":"https://doi.org/10.1002/ctd2.341","url":null,"abstract":"<p>Exosomes are nano-scale vesicles involved in intercellular communication and have a significant role in cancer progression. Tetraspanins, are transmembrane proteins enriched in exosomes. These proteins have significant role in exosome biogenesis, cargo sorting,and target-cell interactions, influencing tumor development and therapeutic response. Exosomal tetraspanins, including CD9, CD63, CD81, and Tspan8, contribute to tumor cell proliferation, angiogenesis, extracellular matrix remodelling, immune evasion, and promote metastasis. Their ability to prepare distant organ sites for colonization highlights their role in establishing the premetastatic niche. Expression profiling of exosomal tetraspanin proteins in cancer become a promising diagnostic and prognostic biomarker. Exosomal tetraspanin proteins also be an effective therapeutic target in cancer.This article highlighted impactful role ofexosomal tetraspanin Proteins in Cancer.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.341","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141639518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and translational research on cancer of the stomach and gastroesophageal junction: A pathologist's view","authors":"Christoph Röcken","doi":"10.1002/ctd2.332","DOIUrl":"https://doi.org/10.1002/ctd2.332","url":null,"abstract":"<p>Adenocarcinomas of the stomach and gastroesophageal junction remain one of the most common malignant tumours in humans worldwide, often with a poor prognosis. Particularly in countries without upper gastrointestinal tract screening endoscopy, tumours that have been asymptomatic for a long time are only diagnosed at an advanced stage. This limits the therapeutic options. Often only palliative therapy concepts are available. Great progress has been made in the last two decades. The genetic basis of adenocarcinomas of the stomach and gastroesophageal junction has been deciphered and new targeted drugs have been developed. Cell and tissue-based predictive diagnostics are becoming increasingly important in therapy planning. Here, surgical pathology forms an important link between basic research, clinical trials, and translation into clinical application. This review article summarizes the experiences made in translational tumour research, which point to the problems of spatial and temporal intratumoral heterogeneity of adenocarcinomas of the stomach and gastroesophageal, the development and continuous re-assessment of therapeutically relevant cut-off values, resistance mechanisms, tumour microenvironment, sexual dimorphism and the pitfalls molecular tumour boards may face.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"4 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.332","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141608091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}