Enhancing the anti-tumor response by combining DNA damage repair inhibitors in the treatment of solid tumors

Yu, Xianzhe; Zhu, Lingling; Wang, Ting; Lü, Li; Liu, Jiewei; Che, Guowei; Zhang, Qinghua

doi:10.1016/j.bbcan.2023.188910

Cited by 3 publications

(4 citation statements)

References 183 publications

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“…DNA damage repair mechanisms play a crucial role in maintaining genomic stability in normal cells. However, hyperactive repair systems in tumor cells might be a fundamental cause of drug resistance (86). For instance, EZH2 facilitates platinum resistance in SCLC by stabilizing DDB2 and promoting NER (61).…”

Section: Dna Damage Repairmentioning

confidence: 99%

Role and potential therapeutic value of histone methyltransferases in drug resistance mechanisms in lung cancer

Zhang,

Shi

et al. 2024

Front. Oncol.

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Lung cancer, ranking second globally in both incidence and high mortality among common malignant tumors, presents a significant challenge with frequent occurrences of drug resistance despite the continuous emergence of novel therapeutic agents. This exacerbates disease progression, tumor recurrence, and ultimately leads to poor prognosis. Beyond acquired resistance due to genetic mutations, mounting evidence suggests a critical role of epigenetic mechanisms in this process. Numerous studies have indicated abnormal expression of Histone Methyltransferases (HMTs) in lung cancer, with the abnormal activation of certain HMTs closely linked to drug resistance. HMTs mediate drug tolerance in lung cancer through pathways involving alterations in cellular metabolism, upregulation of cancer stem cell-related genes, promotion of epithelial-mesenchymal transition, and enhanced migratory capabilities. The use of HMT inhibitors also opens new avenues for lung cancer treatment, and targeting HMTs may contribute to reversing drug resistance. This comprehensive review delves into the pivotal roles and molecular mechanisms of HMTs in drug resistance in lung cancer, offering a fresh perspective on therapeutic strategies. By thoroughly examining treatment approaches, it provides new insights into understanding drug resistance in lung cancer, supporting personalized treatment, fostering drug development, and propelling lung cancer therapy into novel territories.

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Section: Dna Damage Repairmentioning

confidence: 99%

Role and potential therapeutic value of histone methyltransferases in drug resistance mechanisms in lung cancer

Zhang,

Shi

et al. 2024

Front. Oncol.

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“…DDRIs have been developed to target cancers with existing defects in DNA repair [ 112 ]. Poly(ADP-ribose) polymerase (PARP) is critical in DNA repair pathways.…”

Section: Representative Repurposed Drug Candidates To Overcome Ici Re...mentioning

confidence: 99%

“…Tumors with defective homologous recombination, particularly BRCA mutation, are susceptible to PARP inhibitors [ 113 ]. Apart from being used as a monotherapy in cancer treatment, DDRIs were also reported to produce synergistic effects with other anti-tumor treatment modalities or reverse acquired treatment resistance [ 112 ].…”

Section: Representative Repurposed Drug Candidates To Overcome Ici Re...mentioning

confidence: 99%

Drug Repurposing to Circumvent Immune Checkpoint Inhibitor Resistance in Cancer Immunotherapy

To,

Cho

2023

Pharmaceutics

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Immune checkpoint inhibitors (ICI) have achieved unprecedented clinical success in cancer treatment. However, drug resistance to ICI therapy is a major hurdle that prevents cancer patients from responding to the treatment or having durable disease control. Drug repurposing refers to the application of clinically approved drugs, with characterized pharmacological properties and known adverse effect profiles, to new indications. It has also emerged as a promising strategy to overcome drug resistance. In this review, we summarized the latest research about drug repurposing to overcome ICI resistance. Repurposed drugs work by either exerting immunostimulatory activities or abolishing the immunosuppressive tumor microenvironment (TME). Compared to the de novo drug design strategy, they provide novel and affordable treatment options to enhance cancer immunotherapy that can be readily evaluated in the clinic. Biomarkers are exploited to identify the right patient population to benefit from the repurposed drugs and drug combinations. Phenotypic screening of chemical libraries has been conducted to search for T-cell-modifying drugs. Genomics and integrated bioinformatics analysis, artificial intelligence, machine and deep learning approaches are employed to identify novel modulators of the immunosuppressive TME.

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“…First, they provide tools for finding new biomarkers of cancer of a specific type. Second, they help to unravel regulatory networks and signaling pathways that are behind carcinogenesis or cancer response to treatment, with respect to cancer metabolism, DNA damage detection, and repair mechanisms as well as overcoming cell cycle checkpoints [38]. That, in turn, facilitates the development of better treatment protocols and overcoming treatment resistance.…”

Section: Sample Molecular Players Involved In Tumor Response To Treat...mentioning

confidence: 99%

Mathematical Modeling Support for Lung Cancer Therapy—A Short Review

Smieja

2023

IJMS

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The paper presents a review of models that can be used to describe dynamics of lung cancer growth and its response to treatment at both cell population and intracellular processes levels. To address the latter, models of signaling pathways associated with cellular responses to treatment are overviewed. First, treatment options for lung cancer are discussed, and main signaling pathways and regulatory networks are briefly reviewed. Then, approaches used to model specific therapies are discussed. Following that, models of intracellular processes that are crucial in responses to therapies are presented. The paper is concluded with a discussion of the applicability of the presented approaches in the context of lung cancer.

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Enhancing the anti-tumor response by combining DNA damage repair inhibitors in the treatment of solid tumors

Cited by 3 publications

References 183 publications

Role and potential therapeutic value of histone methyltransferases in drug resistance mechanisms in lung cancer

Role and potential therapeutic value of histone methyltransferases in drug resistance mechanisms in lung cancer

Drug Repurposing to Circumvent Immune Checkpoint Inhibitor Resistance in Cancer Immunotherapy

Mathematical Modeling Support for Lung Cancer Therapy—A Short Review

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