Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Cracking the Code: Understanding Cancer’s Defense against Topoisomerase-Active Drugs: A Comprehensive Review

Nilesh Kumar Sharma
ORCID logo ,
Anjali Bahot
,
Gopinath Sekar
,
Mahima Bansode
,
Kratika Khunteta
,
Priyanka Vijay Sonar
,
Ameya Hebale
,
Vaishnavi Salokhe
,
Birandra K. Sinha
*
Version 1 : Received: 16 December 2023 / Approved: 18 December 2023 / Online: 18 December 2023 (13:52:10 CET)

How to cite: Kumar Sharma, N.; Bahot, A.; Sekar, G.; Bansode, M.; Khunteta, K.; Vijay Sonar, P.; Hebale, A.; Salokhe, V.; Sinha, B. K. Cracking the Code: Understanding Cancer’s Defense against Topoisomerase-Active Drugs: A Comprehensive Review. Preprints 2023, 2023121293. https://doi.org/10.20944/preprints202312.1293.v1 Kumar Sharma, N.; Bahot, A.; Sekar, G.; Bansode, M.; Khunteta, K.; Vijay Sonar, P.; Hebale, A.; Salokhe, V.; Sinha, B. K. Cracking the Code: Understanding Cancer’s Defense against Topoisomerase-Active Drugs: A Comprehensive Review. Preprints 2023, 2023121293. https://doi.org/10.20944/preprints202312.1293.v1

Abstract

In recent years, the emergence of cancer drug resistance is one of the crucial tumor hallmarks which is supported by the level of genetic heterogeneity and complexities at cellular levels. Oxidative stress, immune evasion, metabolic reprogramming, overexpression of ABC transporters and stemness are among the several key contributing molecular and cellular response mechanisms. Topo-active drugs, e.g., doxorubicin and topotecan, are clinically active and are utilized extensively against a wide variety of human tumors and often results in the development of resistance and failure to therapy. Thus, there is an urgent need for an incremental and comprehensive understanding of mechanisms of cancer drug resistance specifically in the context of topo-active drugs. This review delves into the intricate mechanistic aspects of these intracellular and extracellular topo-active drug resistance mechanisms and explores use of potential combinatorial approaches by utilizing various topo-active drugs and inhibitors of pathways involved in drug resistance. We believe that this review will help guide basic scientists, pre-clinicians, clinicians, and policymakers toward holistic and interdisciplinary strategies that transcend resistance, renewing optimism in the ongoing battle against cancer.

Keywords

Topoisomerases; Drug resistance; Molecular heterogeneity; Neoplasms; Combinatorial approaches

Subject

Biology and Life Sciences, Life Sciences

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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