Jon Zugazagoitia1, Cristiano Guedes2, Santiago Ponce1, Irene Ferrer3, Sonia Molina-Pinelo3, Luis Paz-Ares4. 1. Medical Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain; Instituto de Investigación I+12. Lung Cancer Clinical Research Unit CNIO, I+12, Madrid, Spain. 2. Medical Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain. 3. Instituto de Investigación I+12. Lung Cancer Clinical Research Unit CNIO, I+12, Madrid, Spain. 4. Medical Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain; Instituto de Investigación I+12. Lung Cancer Clinical Research Unit CNIO, I+12, Madrid, Spain. Electronic address: lpazaresr@seom.org.
Abstract
PURPOSE: In this review, we highlight the current concepts and discuss some of the current challenges and future prospects in cancer therapy. We frequently use the example of lung cancer. METHODS: We conducted a nonsystematic PubMed search, selecting the most comprehensive and relevant research articles, clinical trials, translational papers, and review articles on precision oncology and immuno-oncology. Papers were prioritized and selected based on their originality and potential clinical applicability. FINDINGS: Two major revolutions have changed cancer treatment paradigms in the past few years: targeting actionable alterations in oncogene-driven cancers and immuno-oncology. Important challenges are still ongoing in both fields of cancer therapy. On the one hand, druggable genomic alterations are diverse and represent only small subsets of patients in certain tumor types, which limits testing their clinical impact in biomarker-driven clinical trials. Next-generation sequencing technologies are increasingly being implemented for molecular prescreening in clinical research, but issues regarding clinical interpretation of large genomic data make their wide clinical use difficult. Further, dealing with tumor heterogeneity and acquired resistance is probably the main limitation for the success of precision oncology. On the other hand, long-term survival benefits with immune checkpoint inhibitors (anti-programmed death cell protein-1/programmed death cell ligand-1[PD-1/L1] and anti-cytotoxic T lymphocyte antigen-4 monoclonal antibodies) are restricted to a minority of patients, and no predictive markers are yet robustly validated that could help us recognize these subsets and optimize treatment delivery and selection. To achieve long-term survival benefits, drug combinations targeting several molecular alterations or cancer hallmarks might be needed. This will probably be one of the most challenging but promising precision cancer treatment strategies in the future. IMPLICATIONS: Targeting single molecular abnormalities or cancer pathways has achieved good clinical responses that have modestly affected survival in some cancers. However, this approach to cancer treatment is still reductionist, and many challenges need to be met to improve treatment outcomes with our patients.
PURPOSE: In this review, we highlight the current concepts and discuss some of the current challenges and future prospects in cancer therapy. We frequently use the example of lung cancer. METHODS: We conducted a nonsystematic PubMed search, selecting the most comprehensive and relevant research articles, clinical trials, translational papers, and review articles on precision oncology and immuno-oncology. Papers were prioritized and selected based on their originality and potential clinical applicability. FINDINGS: Two major revolutions have changed cancer treatment paradigms in the past few years: targeting actionable alterations in oncogene-driven cancers and immuno-oncology. Important challenges are still ongoing in both fields of cancer therapy. On the one hand, druggable genomic alterations are diverse and represent only small subsets of patients in certain tumor types, which limits testing their clinical impact in biomarker-driven clinical trials. Next-generation sequencing technologies are increasingly being implemented for molecular prescreening in clinical research, but issues regarding clinical interpretation of large genomic data make their wide clinical use difficult. Further, dealing with tumor heterogeneity and acquired resistance is probably the main limitation for the success of precision oncology. On the other hand, long-term survival benefits with immune checkpoint inhibitors (anti-programmed death cell protein-1/programmed death cell ligand-1[PD-1/L1] and anti-cytotoxic T lymphocyte antigen-4 monoclonal antibodies) are restricted to a minority of patients, and no predictive markers are yet robustly validated that could help us recognize these subsets and optimize treatment delivery and selection. To achieve long-term survival benefits, drug combinations targeting several molecular alterations or cancer hallmarks might be needed. This will probably be one of the most challenging but promising precision cancer treatment strategies in the future. IMPLICATIONS: Targeting single molecular abnormalities or cancer pathways has achieved good clinical responses that have modestly affected survival in some cancers. However, this approach to cancer treatment is still reductionist, and many challenges need to be met to improve treatment outcomes with our patients.
Authors: Shenjie Zhang; Xiyuan Yao; Noah H Watkins; P Keegan Rose; Sofia R Caruso; Cynthia S Day; Ulrich Bierbach Journal: Angew Chem Int Ed Engl Date: 2020-09-29 Impact factor: 15.336