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Review
. 2024 Jan;7(1):e1945.
doi: 10.1002/cnr2.1945. Epub 2023 Nov 22.

Improving targeted small molecule drugs to overcome chemotherapy resistance

Amirhossein Rismanbaf  1
Affiliations
Review

Improving targeted small molecule drugs to overcome chemotherapy resistance

Amirhossein Rismanbaf. Cancer Rep (Hoboken). 2024 Jan.

Abstract

Background: Conventional cancer treatments face the challenge of therapeutic resistance, which causes poor treatment outcomes. The use of combination therapies can improve treatment results in patients and is one of the solutions to overcome this challenge. Chemotherapy is one of the conventional treatments that, due to the non-targeted and lack of specificity in targeting cancer cells, can cause serious complications in the short and long-term for patients by damaging healthy cells. Also, the employment of a wide range of strategies for chemotherapy resistance by cancer cells, metastasis, and cancer recurrence create serious problems to achieve the desired results of chemotherapy. Accordingly, targeted therapies can be used as a combination treatment with chemotherapy to both cause less damage to healthy cells, which as a result, they reduce the side effects of chemotherapy, and by targeting the factors that cause therapeutic challenges, can improve the results of chemotherapy in patients.

Recent findings: Small molecules are one of the main targeted therapies that can be used for diverse targets in cancer treatment due to their penetration ability and characteristics. However, small molecules in cancer treatment are facing obstacles that a better understanding of cancer biology, as well as the mechanisms and factors involved in chemotherapy resistance, can lead to the improvement of this type of major targeted therapy.

Conclusion: In this review article, at first, the challenges that lead to not achieving the desired results in chemotherapy and how cancer cells can be resistant to chemotherapy are examined, and at the end, research areas are suggested that more focusing on them, can lead to the improvement of the results of using targeted small molecules as an adjunctive treatment for chemotherapy in the conditions of chemotherapy resistance and metastasis of cancer cells.

Keywords: DNA repair mechanisms; cancer stem cell; chemotherapy resistance; immunomodulation; small molecule; tumor microenvironment.

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Conflict of interest statement

The authors have stated explicitly that there are no conflicts of interest in connection with this article.

Figures

FIGURE 1
FIGURE 1
Approved targeted small molecule drugs by the FDA for cancer treatment from 2001 to 2021.
FIGURE 2
FIGURE 2
Normal fibroblasts (NFs) conversion into cancer‐associated fibroblasts (CAFs) and the role of CAFs in drug resistance.
FIGURE 3
FIGURE 3
Performance of DNA repair mechanism pathways against camptothecin, etoposide, and cisplatin.
See this image and copyright information in PMC

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