Portal de Periódicos da CAPES

Polytherapy and Targeted Cancer Drug Resistance

2019; Elsevier BV; Volume: 5; Issue: 3 Linguagem: Inglês

10.1016/j.trecan.2019.02.003

2405-8033

Nilanjana Chatterjee, Trever G. Bivona,

Colorectal Cancer Treatments and Studies

The emergence of drug resistance is a barrier to effective cancer treatment. Resistance develops during chemotherapy, radiotherapy, molecularly targeted therapy, and immunotherapy in most patients with cancer and prevents their long-term survival. Multiple mechanisms can promote the emergence of drug resistance and therapy failure. While gene mutations pre-existing in the tumor or acquired during therapy can drive drug resistance, cancers can also evade drug response through nongenetic and epigenetic mechanisms. Other mechanisms contributing to therapy resistance include tumor microenvironment influences, which can modify both drug exposure and response, and tumor heterogeneity within or between patients that underlies varied or minimal therapy response. Cancer drug resistance is multifactorial and evolves dynamically. Tumors evolve rapidly and studying how they adapt or change during therapy could be the key to tackling drug resistance. There is a need to recognize that drug sensitivity and resistance in cancer, and the various resistance mechanisms are not mutually exclusive but can operate together within the same tumor, or across different metastatic tumors in an individual patient. This reality must be considered in designing therapies and determining therapy duration, drug dosing, and timing for deployment of monotherapy or combination therapy. An upfront combination therapy that prevents or delays the evolution of tumors and/or dynamic switching of polytherapies during the initial tumor response before resistance fully emerges holds promise for more effectively attenuating drug resistance to increase patient survival. A current challenge in cancer treatment is drug resistance. Even the most effective therapies often fail to produce a complete and durable tumor response and ultimately give rise to therapy resistance and tumor relapse. However, how resistance arises in cancer remains incompletely understood. While drug resistance in cancer is thought to be driven by irreversible genetic mutations, emerging evidence also implicates reversible proteomic and epigenetic mechanisms in the development of drug resistance. Tumor microenvironment-mediated mechanisms and tumor heterogeneity can significantly contribute to cancer treatment resistance. Here, we discuss the diverse and dynamic strategies that cancers use to evade drug response, the promise of upfront combination and intermittent therapies and therapy switching in forestalling resistance, and epigenetic reprogramming to combat resistance. A current challenge in cancer treatment is drug resistance. Even the most effective therapies often fail to produce a complete and durable tumor response and ultimately give rise to therapy resistance and tumor relapse. However, how resistance arises in cancer remains incompletely understood. While drug resistance in cancer is thought to be driven by irreversible genetic mutations, emerging evidence also implicates reversible proteomic and epigenetic mechanisms in the development of drug resistance. Tumor microenvironment-mediated mechanisms and tumor heterogeneity can significantly contribute to cancer treatment resistance. 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