Adaptive therapy to circumvent drug resistance to tyrosine kinase inhibitors in cancer: is it clinically relevant?

Expert Rev Anticancer Ther. 2022 Dec;22(12):1309-1323. doi: 10.1080/14737140.2022.2147671. Epub 2022 Nov 24.

Abstract

Introduction: Cancer is highly adaptable and is constantly evolving against current targeted therapies such as tyrosine kinase inhibitors. Despite advances in recent decades, the emergence of drug resistance to tyrosine kinase inhibitors constantly hampers therapeutic efficacy of cancer treatment. Continuous therapy versus intermittent clinical regimen has been a debate in drug administration of cancer patients. An ecologically-inspired shift in cancer treatment known as 'adaptive therapy' intends to improve the drug administration of drugs to cancer patients that can delay emergence of drug resistance.

Areas covered: We discuss improved understanding of the concept of drug resistance, the basis of continuous therapy, intermittent clinical regimens, and adaptive therapy will be reviewed. In addition, we discuss how adaptive therapy provides guidance for future cancer treatment.

Expert opinion: The current understanding of drug resistance in cancer leads to poor prognosis and limited treatment options in patients. Fighting drug resistance mutants is constantly followed by new forms of resistance. In most reported cases, continuous therapy leads to drug resistance and an intermittent clinical regimen vaguely delays it. However, adaptive therapy, conceptually, exploits multiple parameters that can suppress the growth of drug resistance and provides safe treatment for cancer patients in the future.

Keywords: Adaptive therapy; clinical treatment; drug resistance; mathematical modelling; non-conventional dosing; tyrosine kinase inhibitors.

MeSH terms

  • Drug Resistance
  • Humans
  • Neoplasms* / drug therapy
  • Tyrosine Kinase Inhibitors*

Substances

  • Tyrosine Kinase Inhibitors