Abstract
Development of targeted therapies in recent years revealed several nonchemotherapeutic options for patients. Chief among targeted therapies is small molecule kinase inhibitors targeting key oncogenic signaling proteins. Through competitive and noncompetitive inhibition of these kinases, and therefore the pathways they activate, cancers can be slowed or completely eradicated, leading to partial or complete remissions for many cancer types. Unfortunately, for many patients, resistance to targeted therapies, such as kinase inhibitors, ultimately develops and can necessitate multiple lines of treatment. Drug resistance can either be de novo or acquired after months or years of drug exposure. Since resistance can be due to several unique mechanisms, there is no one-size-fits-all solution to this problem. However, combinations that target complimentary pathways or potential escape mechanisms appear to be more effective than sequential therapy. Combinations of single kinase inhibitors or alternately multikinase inhibitor drugs could be used to achieve this goal. Understanding how to efficiently target cancer cells and overcome resistance to prior lines of therapy became imperative to the success of cancer treatment. Due to the complexity of cancer, effective treatment options in the future will likely require mixing and matching these approaches in different cancer types and different disease stages.
Highlights
One important example is ibrutinib, a small molecule designed to target Bruton’s tyrosine kinase (BTK) that was successfully used in clinical practice for the treatment of chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and Waldenstrom’s macroglobulinemia
Each of the kinase inhibitor groups discussed here are meant to serve as a brief overview as they could each become their own independent review and this review focused on the pros and cons of different targeted therapeutic strategies rather than exhaustively covering all targeted therapeutics (Table 4)
Specificity sounds attractive for drug development; most view as on they eachofbecome own independent reviewinhibitor and thisgroups review focused thecould pros and cons differenttheir targeted therapeutic strategies rather than ex‐discussed
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Biomedicines 2021, 9, 1591 ing one kinase in a pathway), nonselective (targeting multiple kinases simultaneously), or can be used in combination with other cancer therapeutics: two selective kinase inhibitors working synergistically to allow a stronger effect against the tumor with less toxicity for the patient [5]. While specificity sounds attractive for drug development, most cancers have multiple aberrant pathway activation and can often find simple ways to evade very selective targeted inhibition [2,3,4,5,6]. This review is not meant to be an exhaustive list of all targeted therapies available but a concise and comprehensive set of examples of different treatment strategies to discuss the pros and cons of each
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