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.
Article highlights
Drug resistance to tyrosine kinase inhibitors can exist in the form of evolutionary acquired resistance or pre-existing (de novo) mutations.
High doses of continuous therapy kill most of the drug-sensitive cells; eventually, all of them but select for the growth of drug-resistant cells.
Intermittent clinical regimens allow some treatment-free periods, with rigid treatment schedules able to ease adverse drug reactions and vaguely prolong the emergence of drug-resistant cells.
Adaptive therapy showed that drug-resistant cancer cells are manageable by elongating the treatment-free period with varying drug doses to allow cellular competition instead of killing all drug-sensitive cells.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.