Recent Developments in Combination Chemotherapy for Colorectal and Breast Cancers with Topoisomerase Inhibitors

Sep 24, 2026

Uploaded by Levi

DNA topoisomerases are key enzymes that stabilize DNA supercoiling and resolve entanglements through type I (single-strand breaks) and type II (double-strand breaks) activity, which becomes heightened in rapidly dividing cancer cells. Topoisomerase inhibitors offer established chemotherapeutic benefit, and combination regimens may enhance efficacy while reducing resistance and adverse effects. This review analyzes the clinical landscape for irinotecan with doxorubicin and presents a novel combination therapy approach.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages17

Reading Time43 min

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Introduction

DNA Topoisomerases and Cancer Relevance

Clinical Topoisomerase-Targeting Drugs and Limitations

Rationale for Combination Therapy

Review Recent Developments in Combination Chemotherapy for Colorectal and Breast Cancers with Topoisomerase Inhibitors Jung Yoon Jang 1, Donghwan Kim 2 and Nam Deuk Kim 1, * 1 Department of Pharmacy, College of Pharmacy, Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of Korea; [jungyoon486@pusan.ac.kr](jungyoon486@pusan.ac.kr) 2 Functional Food Materials Research Group, Korea Food Research Institute, Wanju-gun 55365, Republic of Korea; [kimd@kfri.re.kr](kimd@kfri.re.kr) * [Correspondence: nadkim@pusan.ac.kr](Correspondence: nadkim@pusan.ac.kr); Tel.: +82-51-510-2801; Fax: +82-51-513-6754 Abstract: DNA topoisomerases are important enzymes that stabilize DNA supercoiling and resolve entanglements. There are two main types of topoisomerases in all cells: type I, which causes singlestranded DNA breaks, and type II, which cuts double-stranded DNA. Topoisomerase activity is particularly increased in rapidly dividing cells, such as cancer cells. Topoisomerase inhibitors have been an effective chemotherapeutic option for the treatment of several cancers. In addition, combination cancer therapy with topoisomerase inhibitors may increase therapeutic efﬁcacy and decrease resistance or side effects. Topoisomerase inhibitors are currently being used worldwide, including in the United States, and clinical trials on the combination of topoisomerase inhibitors with other drugs are currently underway. The primary objective of this review was to comprehensively analyze the current clinical landscape concerning the combined application of irinotecan, an extensively investigated type I topoisomerase inhibitor for colorectal cancer, and doxorubicin, an extensively researched type II topoisomerase inhibitor for breast cancer, while presenting a novel approach for cancer therapy. Citation: Jang, J.Y.; Kim, D.; Kim, N.D. Recent Developments in Combination Chemotherapy for Colorectal and Breast Cancers with Topoisomerase Inhibitors. Int. J. Mol. Sci. 2023, 24, 8457. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/ijms24098457](10.3390/ijms24098457) Academic Editors: Po-Lin Liao and Tsung-Yun Liu Received: 28 March 2023 Revised: 1 May 2023 Accepted: 7 May 2023 Published: 8 May 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . Keywords: topoisomerases; irinotecan; doxorubicin; clinical trial; combination chemotherapy regimens 1. Introduction Cancer is expected to become the leading cause of death and the most signiﬁcant barrier to increasing life expectancy worldwide in the 21st century [1] . Cancer is an important public health issue worldwide and ranks second among the causes of death in the United States. In 2023, 1,958,310 new cancer cases and 609,820 cancer-related deaths are expected in the United States [2] . Therefore, the development of novel and more speciﬁc chemotherapeutic agents against the most aggressive tumors and the identiﬁcation of new biological targets are vital goals in cancer research [1,3] . One of the main drug targets used in chemotherapy to inhibit the abnormal proliferation of cancer cells is topoisomerase (TOPO) [4] . DNA TOPOs are a group of enzymes that regulate DNA topology. TOPO activity increases especially in rapidly dividing cancer cells [5] . They are involved in many important cellular biological processes, including DNA replication, transcription, recombination, and chromosome condensation [6] . These enzymes covalently attach to groups of DNA phosphorus, causing the DNA strands to split and ﬁnally recombine [5] . Depending on the number of DNA strands cut, TOPO can be classiﬁed into types I and II. Type I enzyme

FAQs

Why are topoisomerases important in cancer therapy?

Topoisomerases control DNA topology and their activity increases in rapidly dividing cells such as cancer cells. Inhibition can damage DNA and support cancer cell death.

How do type I and type II topoisomerases differ?

Type I topoisomerases cleave single DNA strands, while type II enzymes cleave both strands. This distinction determines how supercoiling and entanglements are resolved.

What is the main advantage expected from combination chemotherapy using topoisomerase inhibitors?

Combining agents can improve efficacy over monotherapy by targeting key pathways synergistically or additively. It may also reduce drug resistance and potentially lessen side effects.

Sep 24, 2026

Uploaded by Levi