title: Approaches to modernize the combination drug development paradigm.
abstract: Recent advances in genomic sequencing and omics-based capabilities are uncovering tremendous therapeutic opportunities and rapidly transforming the field of cancer medicine. Molecularly targeted agents aim to exploit key tumor-specific vulnerabilities such as oncogenic or non-oncogenic addiction and synthetic lethality. Additionally, immunotherapies targeting the host immune system are proving to be another promising and complementary approach. Owing to substantial tumor genomic and immunologic complexities, combination strategies are likely to be required to adequately disrupt intricate molecular interactions and provide meaningful long-term benefit to patients. To optimize the therapeutic success and application of combination therapies, systematic scientific discovery will need to be coupled with novel and efficient clinical trial approaches. Indeed, a paradigm shift is required to drive precision medicine forward, from the traditional "drug-centric" model of clinical development in pursuit of small incremental benefits in large heterogeneous groups of patients, to a "strategy-centric" model to provide customized transformative treatments in molecularly stratified subsets of patients or even in individual patients. Crucially, to combat the numerous challenges facing combination drug development-including our growing but incomplete understanding of tumor biology, technical and informatics limitations, and escalating financial costs-aligned goals and multidisciplinary collaboration are imperative to collectively harness knowledge and fuel continual innovation.
authors: Drug Development Program, Division of Medical Oncology & Hematology, Princess Margaret Cancer Centre, Toronto, Ontario, M5G 2M9, Canada.|Department of Medicine, University of Toronto, Toronto, Ontario, M5S 1A8, Canada.|OICR Research Fellow, Ontario Institute for Cancer Research, Toronto, Ontario, M5G 0A3, Canada.
authors: Daphne
authors: D
authors: Day
authors: Drug Development Program, Division of Medical Oncology & Hematology, Princess Margaret Cancer Centre, Toronto, Ontario, M5G 2M9, Canada. lillian.siu@uhn.ca.|Department of Medicine, University of Toronto, Toronto, Ontario, M5S 1A8, Canada. lillian.siu@uhn.ca.
authors: Lillian L
authors: LL
authors: Siu
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics; D002986:Clinical Trials as Topic; D015195:Drug Design; D055808:Drug Discovery; D023281:Genomics / Q000379:methods; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods* / Q000639:trends; D009369:Neoplasms / Q000188:drug therapy*; D057285:Precision Medicine / Q000379:methods* / Q000639:trends
chemical_list: D014408:Biomarkers, Tumor