Precision cancer medicine最新文献

{"title":"FDA-led consortium studies advance quality control of targeted next generation sequencing assays for precision oncology.","authors":"Dan Li, Rebecca Kusko, Baitang Ning, Weida Tong, Donald J Johann, Joshua Xu","doi":"10.21037/pcm-21-29","DOIUrl":"10.21037/pcm-21-29","url":null,"abstract":"<p><p>Cancer is the second leading cause of mortality worldwide despite tremendous advances in treatment. The promise of precision oncology depends on accurate characterization of tumor mutations and subsequent therapy selection. The lack of tumor reference samples along with the associated next generation sequencing (NGS) technical assessments has hindered the development of NGS assays and the realization of benefits for precision oncology. The summarized results and recommendations of several seminal SEQC2 studies along with a vision of the changing landscape of precision oncology and anticipated next steps by the SEQC2 consortium are reported. Importantly, these studies utilized a new robust reference sample material which was developed and constructed to support multiple DNA and RNA-based NGS assay studies. These studies focused on a wide variety of precision oncology assay scenarios and provided guidelines for standardized analyses and best practice recommendations. The evolving landscape of precision oncology requires insights into critical factors supporting the sensitivity and reproducibility of clinical NGS assays for continued improvement in patient outcomes. Persistent development of robust reference materials, quantitative performance metrics, and actionable data analysis recommendations are needed. This series of SEQC2 studies serve to advance NGS-based assays for precision oncology and support regulatory science endeavors.</p>","PeriodicalId":74487,"journal":{"name":"Precision cancer medicine","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41880884","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":"A narrative review of genetic factors affecting fluoropyrimidine toxicity.","authors":"William H Gmeiner","doi":"10.21037/pcm-21-17","DOIUrl":"10.21037/pcm-21-17","url":null,"abstract":"<p><strong>Objective: </strong>Our objective is to document progress in developing personalized therapy with fluoropyrimidine drugs (FPs) to improve outcomes for cancer patients and to identify areas requiring further investigation.</p><p><strong>Background: </strong>FPs including 5-fluorouracil (5-FU), are among the most widely used drugs for treating colorectal cancer (CRC) and other gastrointestinal (GI) malignancies. While FPs confer a survival benefit for CRC patients, serious systemic toxicities, including neutropenia, occur in ~30% of patients with lethality in 0.5-1% of patients. While serious systemic toxicities may occur in any patient, patients with polymorphisms in <i>DPYD</i>, which encodes the rate-limiting enzyme for pyrimidine degradation are at very high risk. Other genetic factors affecting risk for 5-FU toxicity, including miR-27a, are under investigation.</p><p><strong>Methods: </strong>Literature used to inform the text of this article was selected from PubMed.gov from the National Library of Medicine while regulatory documents were identified via Google search.</p><p><strong>Conclusions: </strong>Clinical studies to date have validated four <i>DPYD</i> polymorphisms (<i>DPYD</i>*2A, <i>DPYD</i>*13, c.2846A>T, HapB3) associated with serious toxicities in patients treated with 5-FU. Genetic screening for these is being implemented in the Netherlands and the UK and has been shown to be a cost-effective way to improve outcomes. Factors other than <i>DPYD</i> polymorphisms (e.g., miR-27a, <i>TYMS</i>, ENOSF1, p53) also affect 5-FU toxicity. Functional testing for deficient pyrimidine catabolism {defined as [U] >16 ng/mL or [UH2]:[U] <10} is being implemented in France and has demonstrated utility in identifying patients with elevated risk for 5-FU toxicity. Therapeutic drug monitoring (TDM) from plasma levels of 5-FU during first cycle treatment also is being used to improve outcomes and pharmacokinetic-based dosing is being used to increase the percent of patients within optimal area under the curve (AUC) (18-28 mg*h/L) values. Patients maintained in the optimal AUC range experienced significantly reduced systemic toxicities. As understanding the genetic basis for increased risk of 5-FU toxicity becomes more refined, the development of functional-based methods to optimize treatment is likely to become more widespread.</p>","PeriodicalId":74487,"journal":{"name":"Precision cancer medicine","volume":"4 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8f/46/nihms-1732089.PMC8664072.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39720758","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":"Asbestos-induced chronic inflammation in malignant pleural mesothelioma and related therapeutic approaches-a narrative review.","authors":"Alicia A Zolondick,&nbsp;Giovanni Gaudino,&nbsp;Jiaming Xue,&nbsp;Harvey I Pass,&nbsp;Michele Carbone,&nbsp;Haining Yang","doi":"10.21037/pcm-21-12","DOIUrl":"https://doi.org/10.21037/pcm-21-12","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this review is addressing the mechanisms of asbestos carcinogenesis, including chronic inflammation and autophagy-mediated cell survival, and propose potential innovative therapeutic targets to prevent mesothelioma development or improve drug efficacy by reducing inflammation and autophagy.</p><p><strong>Background: </strong>Diffuse malignant pleural mesothelioma is an aggressive cancer predominantly related to chronic inflammation caused by asbestos exposure. Millions of individuals have been exposed to asbestos or to other carcinogenic mineral fibers occupationally or environmentally, resulting in an increased risk of developing mesothelioma. Overall patient survival rates are notably low (about 8-14 months from the time of diagnosis) and mesothelioma is resistant to existing therapies. Additionally, individuals carrying inactivating germline mutations in the BRCA-associated protein 1 (<i>BAP1</i>) gene and other genes are predisposed to developing cancers, prevalently mesothelioma. Their risk of developing mesothelioma further increases upon exposure to asbestos. Recent studies have revealed the mechanisms and the role of inflammation in asbestos carcinogenesis. Biomarkers for asbestos exposure and malignant mesothelioma have also been identified. These findings are leading to the development of novel therapeutic approaches to prevent or delay the growth of mesothelioma.</p><p><strong>Methods: </strong>Review of full length manuscripts published in English from January 1980 to February 2021 gathered from PubMed.gov from the National Center of Biotechnology Information and the National Library of Medicine were used to inform this review.</p><p><strong>Conclusion: </strong>Key regulators of chronic inflammation mediate asbestos-driven mesothelial cell transformation and survival through autophagic pathways. Recent studies have elucidated some of the key mechanisms involved in asbestos-induced chronic inflammation, which are largely driven by extracellular high mobility group box 1 (HMGB1). Upon asbestos exposure, mesothelial cells release HMGB1 from the nucleus to the cytoplasm and extracellular space, where HMGB1 initiates an inflammatory response. HMGB1 translocation and release also activates autophagy and other pro-survival mechanisms, which promotes mesothelioma development. HMGB1 is currently being investigated as a biomarker to detect asbestos exposure and to detect mesothelioma development in its early stage when therapy is more effective. In parallel, several approaches inhibiting HMGB1 activities have been studied and have shown promising results. Moreover, additional cytokines, such as IL-1β and TNF-α are being targeted to interfere with the inflammatory process that drives mesothelioma growth. Developing early detection methods and novel therapeutic strategies is crucial to prolong overall survival of patients with mesothelioma. Novel therapies targeting regulators of asbestos-induced inflamm","PeriodicalId":74487,"journal":{"name":"Precision cancer medicine","volume":"4 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5f/b4/nihms-1737904.PMC8797751.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39573848","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":"Management of acquired resistance to ALK inhibitors: repeat biopsy to characterize mechanisms of resistance significantly impacts clinical outcomes","authors":"A. Hegde, M. Khalil","doi":"10.21037/PCM-21-5","DOIUrl":"https://doi.org/10.21037/PCM-21-5","url":null,"abstract":"The discovery of anaplastic lymphoma kinase (ALK) rearrangements in patients with non-small cell lung cancer (NSCLC) in 2007 and the subsequent development of ALK tyrosine kinase inhibitors (TKI) paved the way for precision oncology in the treatment of NSCLC (1). Crizotinib, a multi-kinase inhibitor with activity against ALK and mesenchymal epithelial transition (MET) receptors, was the first TKI to be approved by the US Food and Drug Administration (FDA) for treatment of ALK-rearranged (ALK+) NSCLC, based on PROFILE1007 and 1014 trials (2,3). The second generation ALK TKIs, ceritinib, alectinib and brigatinib are more selective and potent when compared to crizotinib. Alectinib and brigatinib have demonstrated superior efficacy in patients with ALK+ NSCLC when compared to crizotinib in treatment naïve patients (4-6). Both are now FDA approved for use in treatment naïve patients with ALK+ NSCLC. Ceritinib is also FDA approved in the first line setting based on superior progression free survival (PFS) when compared to platinum doublet chemotherapy (7). Recently, lorlatinib, a third generation ALK inhibitor showed improved PFS compared to crizotinib in treatment naïve patients (8). Moreover, next generation ALK TKIs have superior intracranial efficacy compared to crizotinib. Despite a growing portfolio of selective ALK TKIs, resistance mechanisms inevitably develop and challenges in management of disease progression remain. Herein we discuss the crucial role repeat tumor biopsy has in impacting the clinical outcomes of patients with ALK+ NSCLC. ALK resistance mechanisms and management","PeriodicalId":74487,"journal":{"name":"Precision cancer medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42558602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of pemetrexed-based chemotherapy and radiation therapy in RET-rearranged lung adenocarcinoma: a mono-institutional case series","authors":"F. Citarella, M. Russano, A. Galletti, G. Fazio, B. Vincenzi, G. Tonini, D. Santini","doi":"10.21037/PCM-21-1","DOIUrl":"https://doi.org/10.21037/PCM-21-1","url":null,"abstract":": Rearranged during Transfection gene (RET) fusions occur in 0.7–2% of non-small cell lung cancer (NSCLC) representing a novel target for oncogene addicted disease. Retrospective analyses showed remarkable response to the chemotherapic anti-folate drug Pemetrexed in patients affected by RET-fusion NSCLC, while immunotherapy does not assure remarkable efficacy. Nowadays, novel therapies are enriching the number of specific anti-RET strategies. The present mono-institutional case series reports significant responses to Pemetrexed, and radiation therapies performed on previously identified or oligo-progressing metastatic sites. Next Generation Sequencing conducted on histological tissue in two cases and on blood specimen in one case detected RET fusion in the clinical course after chemotherapy. As other oncogene addicted subtypes of NSCLC, such as EGFR mutated, ALK and ROS1 rearranged, radiation treatment of residual or oligo-progressing lesions appeared to prolong the clinical benefit from oncological treatments. Despite specific anti-RET treatments are under evaluation for RET-positive non squamous NSCLC, Pemetrexed assured optimal and durable clinical response. The addition of loco-regional treatment of residual or oligo-progressive disease prolonged the time to chemotherapy failure. The present manuscript aims at arising the hypothesis that loco-regional treatment could be considered for oligo-metastatic disease with consolidation extent and could allow beyond progression Pemetrexed-based therapy for oligo-progressive disease.","PeriodicalId":74487,"journal":{"name":"Precision cancer medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47639209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ROS-1 NSCLC therapy resistance mechanism","authors":"M. García-Pardo, A. Calles","doi":"10.21037/PCM-20-65","DOIUrl":"https://doi.org/10.21037/PCM-20-65","url":null,"abstract":": ROS1 -rearrangements occur in 1–2% of advanced non-small cell lung cancer (NSCLC) and define a distinct molecular subgroup. In the last decade, the development of molecularly targeted therapy has changed the standard of care for NSCLC patients harboring ROS1 and other driver mutations. The multitargeted MET/ALK/ROS1 tyrosine kinase inhibitor (TKI) crizotinib significantly improves overall survival for these patients; however, resistance to crizotinib invariably occurs, leading to disease progression. Several resistance mechanisms to crizotinib have been reported, including pharmacokinetic/dynamic failure, biological acquired resistance by secondary point mutations in the ROS1 kinase domain, bypass tracks, and phenotypic changes. Next-generation TKIs can be clinically active against ROS1 -rearranged NSCLC after progression to crizotinib, depending on the acquired resistance mechanism, or have substantial intracranial activity compared to crizotinib. Understanding the mechanisms of resistance to ROS1 TKI is critical to develop selective therapies. Thus, contemporary approaches are essential to improve outcomes with subsequent treatments in patients with ROS1 -rearranged lung cancer. Tissue or blood-based next generation sequencing (NGS) can help to identify the resistance mechanism to ROS1 TKI and may be considered after tumor progression in order to better select further lines of targeted therapy, although prospective validation of this therapeutic approach is needed. In this review, we perform a comprehensive analysis of ROS1 fusions in NSCLC, resistance mechanism to ROS1 targeted therapies, and future strategies. have been tested in the first-line. Resistance mechanism to different TKIs used in the front-line treatment other than crizotinib for ROS1 -positive cancer patients can modified subsequent therapies.","PeriodicalId":74487,"journal":{"name":"Precision cancer medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44524130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monitoring therapeutic response and resistance with liquid biopsy","authors":"V. Calvo, A. Romero, M. Provencio","doi":"10.21037/PCM-20-46","DOIUrl":"https://doi.org/10.21037/PCM-20-46","url":null,"abstract":"Lung cancer is the leading cause of cancer-related death in industrialized countries and one of the most common cancers in the world. The most common type of lung cancer is non-small cell lung cancer (NSCLC), which accounts for 80–90%. Approximately 3–7% of NSCLC patients have a genomic rearrangement of the anaplastic lymphoma kinase (ALK) gene. Tyrosine kinase inhibitors (TKIs) of the ALK have significantly improved the quality of life and survival of ALK-positive NSCLC. The therapeutic arsenal includes first-generation ALK-TKI: crizotinib and more recently second-generation ALK-TKI: ceritinib, ensartinib, alectinib and brigatinib and third-generation ALK-TKI: lorlatinib. Second-generation ALKTKIs have become the new standard of care in first-line setting in advanced ALK-positive NSCLC patients. However, most of these patients relapse as the tumor acquires resistance mutations. Although the rebiopsy at the time of ALK-TKI progression is not always feasible, liquid biopsy at progression is a potential alternative tool. Circulating tumor cells (CTCs), circulating free tumor DNA (cfDNA), exosomes and tumor-educated platelets (TEPs) in body fluid could be used to monitor response to treatments and resistance mechanisms, this may provide relevant information to define genomic-driven therapeutic sequences. Even though, the use of ALK-TKI according to the resistance mechanism, at the time of progression, seems the most appropriate, blinded treatment decisions are the most common in the clinic.","PeriodicalId":74487,"journal":{"name":"Precision cancer medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44494442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-small cell lung cancer molecular characterization of advanced disease with focus on sex differences: a narrative review","authors":"R. Bruno, G. Alí, A. Poma, G. Fontanini","doi":"10.21037/PCM-20-72","DOIUrl":"https://doi.org/10.21037/PCM-20-72","url":null,"abstract":"Molecular characterization is the basis of precision medicine in advanced non-small cell lung cancer (NSCLC), especially in the adenocarcinoma subtype. Determination of the molecular status of several predictive biomarkers (EGFR, ALK, ROS1, BRAF, RET, NTRK and PD-L1) is mandatory to tailor the therapy. Nowadays it is extremely clear that the definition of oncogene addiction and the evaluation of single biomarkers are insufficient to fully understand tumor biology and behaviour. In this context, peculiar molecular features with an impact on prognosis and a response to therapy can be related to sex differences. Lung cancer in non-smokers has been reported to be more frequent in women than in men, with a higher rate of driver and targetable alterations. A different molecular picture between men and women can depend on a sex-biased susceptibility to the carcinogenic effects of tobacco exposure and hormonal status. Although lung cancer in women has peculiar biological and clinical features, further studies are needed to better define sex-related molecular aspects and to evaluate to what extent they can improve personalized treatments.","PeriodicalId":74487,"journal":{"name":"Precision cancer medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47052048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Concerns and controversies regarding ipilimumab-based immunotherapy in the first-line treatment of non-small cell lung cancer","authors":"I. Riano, N. Duma","doi":"10.21037/PCM-2020-MNSCLC-08","DOIUrl":"https://doi.org/10.21037/PCM-2020-MNSCLC-08","url":null,"abstract":"© Precision Cancer Medicine. All rights reserved. Precis Cancer Med 2021;4:7 | http://dx.doi.org/10.21037/pcm-2020-mnsclc-08 Ipilimumab is a fully human monoclonal antibody against cytotoxic T-lymphocyte antigen 4 (CTLA-4), which has shown early evidence of longer overall survival (OS) in patients with melanoma (1), renal cell carcinoma (2), and unresectable malignant pleural mesothelioma (3). Furthermore, ipilimumab plus nivolumab has shown antitumor activity in patients with small-cell lung cancer (4). The ipilimumab-based immunotherapy as a first-line treatment of non-small cell lung cancer (NSCLC) has represented a substantial change in therapeutics, particularly for patients with potential low tolerability to conventional chemotherapy. Yet, the extended long-term survival is achieved only in a minority of patients with NSCLC (5-7). Dual checkpoint blockade was associated with durable tumor responses and prolonged survival in patients with advanced NSCLC; however, a higher frequency of adverse events (AEs) was reported with the dual immunotherapy regimen (5,6,8,9). Most of the evidence regarding the development of ipilimumab-based immunotherapy in the first-line treatment of advanced NSCLC derives from two pivotal clinical trials; CheckMate-227 (5) and CheckMate-9LA (6). CheckMate-227 is a randomized, first-line, open-label, phase 3, multi-part trial that explored the efficacy and safety of nivolumab plus ipilimumab, compared with platinum-doublet chemotherapy (5). Eligible participants included patients with squamous or nonsquamous stage IV or recurrent NSCLC. CheckMate 227 is a six-arm trial, divided into two parts. In part 1a, patients with programmed cell death-1 ligand-1 (PD-L1) expression level ≥1% on tumor cells (TCs) were randomly assigned in a 1:1:1 ratio to receive nivolumab [at a dose of 3 mg per kilogram (kg) every two weeks] plus ipilimumab (at a dose of 1 mg per kg every six weeks) vs. nivolumab monotherapy (240 mg every two weeks) vs. platinum doublet chemotherapy (every three weeks for up to 4 cycles). Patients whose tumor express PDL1 <1% were allowed to enroll in the part 1b of the study. Crossover between the treatment groups was not permitted. The primary endpoint was OS (5). A total of 1,189 patients were enrolled in part 1a; 396 were assigned to receive nivolumab plus ipilimumab, 396 to nivolumab monotherapy, and 397 to chemotherapy. Of the 550 patients enrolled in part 1b, 187 were assigned to receive nivolumab plus ipilimumab, 177 nivolumab plus chemotherapy, and 186 chemotherapy. Three-year update from CheckMate-227 part 1 (at a median follow-up of 43.1 months), patients with PD-L1 level ≥1% on TCs showed a survival benefit compared to the chemotherapy arm (HR: 0.79; 95% CI, 0.67–0.93); three-year OS rates were 33% for nivolumab plus ipilimumab and 22% for the chemotherapy alone arm (10). Nivolumab plus ipilimumab also delayed disease progression among these patients, with a three-year progression-free survival (PFS) ","PeriodicalId":74487,"journal":{"name":"Precision cancer medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41649451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of immunotherapy in metastatic triple negative breast cancer: a narrative review of the current clinical trials","authors":"Kim Koczka, N. Nixon","doi":"10.21037/PCM-20-58","DOIUrl":"https://doi.org/10.21037/PCM-20-58","url":null,"abstract":"Triple negative breast cancer is an aggressive subtype of breast cancer that lacks expression of estrogen and progesterone receptors, and does not overexpress the human epithelial growth factor 2 receptor. Triple negative breast cancer occurs in approximately 20% of breast cancer cases, and patients are more likely to present with an advanced stage, have higher relapse rates, and have a worse prognosis than other breast cancer types. There are no targeted therapies for the majority of patients with triple negative breast cancer. The mainstay of treatment remains chemotherapy and the historical median overall survival for metastatic patients is around one year. Immunotherapy has dramatically improved outcomes in other malignancies by harnessing the body’s immune system to attack cancer cells. Triple negative breast cancer is the most immunogenic type of breast cancer, with a large genetic mutational burden and a relatively high number of immune cells found in the cancer microenvironment compared to other breast cancer subtypes. While initial studies of single agent immunotherapy in metastatic triple negative breast cancer were promising, the survival outcomes have been disappointing. Combining systemic therapy with immunotherapy has become a recent focus of clinical trials, and is now the current standard of care for treatment naive metastatic triple negative patients that are programmed death-ligand 1 positive. The efficacy of combined chemoimmunotherapy for first-line treatment has yet to be replicated, and recent clinical data questions the true benefit. This review summarizes the clinical trials of single agent and combination strategies for immunotherapy in metastatic triple negative breast cancer. We also examine the potential role for biomarkers, and future direction of treatment.","PeriodicalId":74487,"journal":{"name":"Precision cancer medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48446329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}