A view on drug resistance in cancer
By N. Vasan, J. Baselga, D. Hyman. Nature, 2019
2,323 citations recorded by the source corpus.
The problem of resistance to therapy in cancer is multifaceted. Here we take a reductionist approach to define and separate the key determinants of drug resistance, which include tumour burden and growth kinetics; tumour heterogeneity; physical barriers; the immune system and the microenvironment; undruggable cancer drivers; and the many consequences of applying therapeutic pressures. We propose four general solutions to drug resistance that are based on earlier detection of tumours permitting cancer interception; adaptive monitoring during therapy; the addition of novel drugs and improved pharmacological principles that result in deeper responses; and the identification of cancer cell dependencies by high-throughput synthetic lethality screens, integration of clinico-genomic data and computational modelling. These different approaches could eventually be synthesized for each tumour at any decision point and used to inform the choice of therapy. A review of drug resistance in cancer analyses each biological determinant of resistance separately and discusses existing and new therapeutic strategies to combat the problem as a whole.
Subfields: Cancer Research, Oncology, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/8b434877ea3d4b74ba06fc09715cf50353ff8450
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In Cancer Research
Citations in the corpus
- SynergyFinder Plus: Toward Better Interpretation and Annotation of Drug Combination Screening Datasets (2022, background): “Many complex diseases including cancer and infectious diseases develop drug resistance [1,2].”
- TISCH2: expanded datasets and new tools for single-cell transcriptome analyses of the tumor microenvironment (2022, background): “Due to the striking genetic and cellular heterogeneity within the TME, only a fraction of patients could benefit from immunotherapy (5,6).”
- Overcoming Endocrine Resistance in Breast Cancer (2020, neutral): “Potential strategies to improve the cure rates of ER+ breast cancers include (i) treatment with the most effective upfront therapy/ combinations to maximize tumor eradication (Vasan et al., 2019) (ie, endocrine therapy + CDK4/6i, PI3Kα inhibitors, etc.”
- Mitochondrial dynamics in health and disease: mechanisms and potential targets (2023, background): “248 Breast cancer stem cells (BCSCs) play a crucial role in chemotherapy resistance and recurrence in breast cancer.”
- NF-κB in biology and targeted therapy: new insights and translational implications (2024, background): “246,247 CD10 + GPR77 + CAF, de fi ned by speci fi c cell surface markers, promotes tumor progression and chemoresistance through sustained activation of NF-κ B signaling and complement signaling and secretion of IL-8 and IL-65 to maintain stemness of tumor stem cells.”