Molecular mechanisms and therapeutic strategies in overcoming chemotherapy resistance in cancer

Abstract Cancer remains a leading cause of mortality globally and a major health burden, with chemotherapy often serving as the primary therapeutic option for patients with advanced-stage disease, partially compensating for the limitations of non-curative treatments. However, the emergence of chemot...

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Main Authors: Yixiang Gu, Ruifeng Yang, Yang Zhang, Miaomiao Guo, Kyle Takehiro, Ming Zhan, Linhua Yang, Hui Wang
Format: Article
Language:English
Published: Springer 2025-01-01
Series:Molecular Biomedicine
Subjects:
Online Access:https://doi.org/10.1186/s43556-024-00239-2
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author Yixiang Gu
Ruifeng Yang
Yang Zhang
Miaomiao Guo
Kyle Takehiro
Ming Zhan
Linhua Yang
Hui Wang
author_facet Yixiang Gu
Ruifeng Yang
Yang Zhang
Miaomiao Guo
Kyle Takehiro
Ming Zhan
Linhua Yang
Hui Wang
author_sort Yixiang Gu
collection DOAJ
description Abstract Cancer remains a leading cause of mortality globally and a major health burden, with chemotherapy often serving as the primary therapeutic option for patients with advanced-stage disease, partially compensating for the limitations of non-curative treatments. However, the emergence of chemotherapy resistance significantly limits its efficacy, posing a major clinical challenge. Moreover, heterogeneity of resistance mechanisms across cancer types complicates the development of universally effective diagnostic and therapeutic approaches. Understanding the molecular mechanisms of chemoresistance and identifying strategies to overcome it are current research focal points. This review provides a comprehensive analysis of the key molecular mechanisms underlying chemotherapy resistance, including drug efflux, enhanced DNA damage repair (DDR), apoptosis evasion, epigenetic modifications, altered intracellular drug metabolism, and the role of cancer stem cells (CSCs). We also examine specific causes of resistance in major cancer types and highlight various molecular targets involved in resistance. Finally, we discuss current strategies aiming at overcoming chemotherapy resistance, such as combination therapies, targeted treatments, and novel drug delivery systems, while proposing future directions for research in this evolving field. By addressing these molecular barriers, this review lays a foundation for the development of more effective cancer therapies aimed at mitigating chemotherapy resistance.
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series Molecular Biomedicine
spelling doaj-art-864188ec142247aab95e06e52e4bdc482025-01-12T12:05:00ZengSpringerMolecular Biomedicine2662-86512025-01-016112210.1186/s43556-024-00239-2Molecular mechanisms and therapeutic strategies in overcoming chemotherapy resistance in cancerYixiang Gu0Ruifeng Yang1Yang Zhang2Miaomiao Guo3Kyle Takehiro4Ming Zhan5Linhua Yang6Hui Wang7Department of Biliary-Pancreatic Surgery, Renji Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Urology, Fudan University Shanghai Cancer CenterDepartment of Biliary-Pancreatic Surgery, Renji Hospital, Shanghai Jiao Tong University School of MedicineThe Core Laboratory in Medical Center of Clinical Research, State Key Laboratory of Medical Genomics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineArcadia High SchoolThe Core Laboratory in Medical Center of Clinical Research, State Key Laboratory of Medical Genomics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Biliary-Pancreatic Surgery, Renji Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Biliary-Pancreatic Surgery, Renji Hospital, Shanghai Jiao Tong University School of MedicineAbstract Cancer remains a leading cause of mortality globally and a major health burden, with chemotherapy often serving as the primary therapeutic option for patients with advanced-stage disease, partially compensating for the limitations of non-curative treatments. However, the emergence of chemotherapy resistance significantly limits its efficacy, posing a major clinical challenge. Moreover, heterogeneity of resistance mechanisms across cancer types complicates the development of universally effective diagnostic and therapeutic approaches. Understanding the molecular mechanisms of chemoresistance and identifying strategies to overcome it are current research focal points. This review provides a comprehensive analysis of the key molecular mechanisms underlying chemotherapy resistance, including drug efflux, enhanced DNA damage repair (DDR), apoptosis evasion, epigenetic modifications, altered intracellular drug metabolism, and the role of cancer stem cells (CSCs). We also examine specific causes of resistance in major cancer types and highlight various molecular targets involved in resistance. Finally, we discuss current strategies aiming at overcoming chemotherapy resistance, such as combination therapies, targeted treatments, and novel drug delivery systems, while proposing future directions for research in this evolving field. By addressing these molecular barriers, this review lays a foundation for the development of more effective cancer therapies aimed at mitigating chemotherapy resistance.https://doi.org/10.1186/s43556-024-00239-2Chemotherapy resistanceMolecular mechanismsApoptosis evasionCancer stem cellsEpigenetic modificationsTargeted therapy
spellingShingle Yixiang Gu
Ruifeng Yang
Yang Zhang
Miaomiao Guo
Kyle Takehiro
Ming Zhan
Linhua Yang
Hui Wang
Molecular mechanisms and therapeutic strategies in overcoming chemotherapy resistance in cancer
Molecular Biomedicine
Chemotherapy resistance
Molecular mechanisms
Apoptosis evasion
Cancer stem cells
Epigenetic modifications
Targeted therapy
title Molecular mechanisms and therapeutic strategies in overcoming chemotherapy resistance in cancer
title_full Molecular mechanisms and therapeutic strategies in overcoming chemotherapy resistance in cancer
title_fullStr Molecular mechanisms and therapeutic strategies in overcoming chemotherapy resistance in cancer
title_full_unstemmed Molecular mechanisms and therapeutic strategies in overcoming chemotherapy resistance in cancer
title_short Molecular mechanisms and therapeutic strategies in overcoming chemotherapy resistance in cancer
title_sort molecular mechanisms and therapeutic strategies in overcoming chemotherapy resistance in cancer
topic Chemotherapy resistance
Molecular mechanisms
Apoptosis evasion
Cancer stem cells
Epigenetic modifications
Targeted therapy
url https://doi.org/10.1186/s43556-024-00239-2
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