Role of microRNAs in regulation of doxorubicin and paclitaxel responses in lung tumor cells - Review

Sep 24, 2026

Lung cancer remains a major global health challenge, with high mortality that persists despite advances in chemotherapy, radiotherapy, and surgery. Doxorubicin and paclitaxel are commonly used first-line agents, yet substantial DOX/TXL resistance drives tumor recurrence and metastasis. Adverse effects in normal tissues make it essential to clarify molecular mechanisms underlying resistance to support reliable prognostic and therapeutic markers. This review summarizes how microRNAs influence DOX/TXL response through signaling pathways, autophagy, transcription factors, and apoptosis, supporting miRNAs as non-invasive biomarkers for predicting treatment outcomes.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Background

Lung cancer burden and survival

Chemotherapy options and resistance challenge

Overview of DOX and TXL actions

Doxorubicin mechanisms

Paclitaxel mechanisms

Role of microRNAs in DOX/TXL response

Regulation of sensitivity and resistance

Pathways involving signaling, autophagy, transcription, and apoptosis

Maharati and Moghbeli Cell Division (2023) 18:11 [https://doi.org/10.1186/s13008-023-00093-8](https://doi.org/10.1186/s13008-023-00093-8) Cell Division REVIEW Open Access Role of microRNAs in regulation of doxorubicin and paclitaxel responses in lung tumor cells Amirhosein Maharati 1 and Meysam Moghbeli2* Abstract Lung cancer as the leading cause of cancer related mortality is always one of the main global health challenges. Despite the recent progresses in therapeutic methods, the mortality rate is still significantly high among lung cancer patients. A wide range of therapeutic methods including chemotherapy, radiotherapy, and surgery are used to treat lung cancer. Doxorubicin (DOX) and Paclitaxel (TXL) are widely used as the first-line chemotherapeutic drugs in lung cancer. However, there is a significant high percentage of DOX/TXL resistance in lung cancer patients, which leads to tumor recurrence and metastasis. Considering, the side effects of these drugs in normal tissues, it is required to clarify the molecular mechanisms of DOX/TXL resistance to introduce the efficient prognostic and therapeutic markers in lung cancer. MicroRNAs (miRNAs) have key roles in regulation of different pathophysiological processes including cell division, apoptosis, migration, and drug resistance. MiRNA deregulations are widely associated with chemo resistance in various cancers. Therefore, considering the importance of miRNAs in chemotherapy response, in the present review, we discussed the role of miRNAs in regulation of DOX/TXL response in lung cancer patients. It has been reported that miRNAs mainly induced DOX/TXL sensitivity in lung tumor cells by the regulation of signaling pathways, autophagy, transcription factors, and apoptosis. This review can be an effective step in introducing miRNAsas the non-invasive prognostic markers to predict DOX/TXL response in lung cancer patients. Keywords Lung cancer, Paclitaxel, Doxorubicin, Chemo resistance, microRNA Background Lung cancer is the most frequent cancer and is responsible for the highest number of cancer-related deaths in the world [1]. Despite the recent progresses in molecular targeted therapies and surgical techniques, the overall 5-years survival rate is still around 15% for lung cancer patients [2]. Non-small cell lung cancer (NSCLC) is the most frequent lung tumor type accounting for 85% of *Correspondence: Meysam Moghbeli [moghbelim@mums.ac.ir](moghbelim@mums.ac.ir) 1 Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran 2 Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran all cases [1, 3]. Targeted drugs have efficient therapeutic benefits for NSCLC patients; however, drug resistance is a frequent challenge that is finally observed among a large proportion of NSCLC patients [4, 5]. Cisplatin, carboplatin, paclitaxel, docetaxel, gemcitabine, and pemetrexed are the frequently used chemotherapeutic options for NSCLC patients [6–8]. DNA-damaging factors are the most commonly used types of chemotherapeutic drugs [9, 10]. They prevent cell proliferation while induce cell death by the suppression of the double-strand breaks rejoining [11]. Microtubule targeting agents (MTAs) are also conventional chemotherapeutic drugs for NSCLC patients. They bind to microtubules at various sites to disrupt their dynamics and structure, resulting in cell cycle arrest and subsequent cell death [12, © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the

FAQs

Why are doxorubicin and paclitaxel important in lung cancer treatment?

They are widely used first-line chemotherapeutic drugs for lung cancer. Their clinical value is challenged by a substantial rate of drug resistance.

What problem does DOX/TXL resistance cause in lung cancer patients?

It contributes to tumor recurrence and metastasis. It also reduces treatment effectiveness and survival.

How do microRNAs affect DOX/TXL responses according to the review?

MicroRNAs influence sensitivity by regulating signaling pathways, autophagy, transcription factors, and apoptosis in lung tumor cells. The review proposes miRNAs as potential non-invasive prognostic markers.

Sep 24, 2026

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