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Review
. 2022 Oct 13;3(4):e181.
doi: 10.1002/mco2.181. eCollection 2022 Dec.

Small molecule inhibitors targeting the cancers

Gui-Hong Liu  1 , Tao Chen  2 , Xin Zhang  1 , Xue-Lei Ma  1 , Hua-Shan Shi  1
Affiliations
Review

Small molecule inhibitors targeting the cancers

Gui-Hong Liu et al. MedComm (2020). .

Abstract

Compared with traditional therapies, targeted therapy has merits in selectivity, efficacy, and tolerability. Small molecule inhibitors are one of the primary targeted therapies for cancer. Due to their advantages in a wide range of targets, convenient medication, and the ability to penetrate into the central nervous system, many efforts have been devoted to developing more small molecule inhibitors. To date, 88 small molecule inhibitors have been approved by the United States Food and Drug Administration to treat cancers. Despite remarkable progress, small molecule inhibitors in cancer treatment still face many obstacles, such as low response rate, short duration of response, toxicity, biomarkers, and resistance. To better promote the development of small molecule inhibitors targeting cancers, we comprehensively reviewed small molecule inhibitors involved in all the approved agents and pivotal drug candidates in clinical trials arranged by the signaling pathways and the classification of small molecule inhibitors. We discussed lessons learned from the development of these agents, the proper strategies to overcome resistance arising from different mechanisms, and combination therapies concerned with small molecule inhibitors. Through our review, we hoped to provide insights and perspectives for the research and development of small molecule inhibitors in cancer treatment.

Keywords: combination therapy; multikinase molecule inhibitors; resistance; small molecule inhibitors; small molecule kinase inhibitors.

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Conflict of interest statement

The authors have no conflict of interest to declare.

Figures

FIGURE 1
FIGURE 1
Timeline for the US FDA‐approved small molecule inhibitors targeting the cancers. Figure created with BioRender.com
FIGURE 2
FIGURE 2
The mechanisms of the US FDA‐approved small molecule inhibitors targeting the cancers. The cell surface receptors and signaling pathways, DNA transcription, DNA damage repair, epigenetic modifications, nuclear transport, blood vessels, and apoptosis are involved in the targets of the US FDA‐approved small molecule inhibitors. Figure created with BioRender.com
FIGURE 3
FIGURE 3
Some of the challenges and future directions of small molecule inhibitors. (A) Approaches to develop small molecule inhibitors with new targets. (B) Factors for adjuvant therapy with small molecule inhibitors. (C) Precautions in the clinical use of small molecule inhibitors. Figure created with BioRender.com
FIGURE 4
FIGURE 4
Mechanisms of secondary resistance of small molecule inhibitors and countermeasures. Figure created with BioRender.com
See this image and copyright information in PMC

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