Recent advances in drug repurposing for cancer immunomodulation - Review - Mechanistic insights and clinical translation

Sep 22, 2026

Drug repurposing offers a faster, lower-cost route to cancer therapy by redirecting FDA-approved drugs to modulate antitumor immunity. This review summarizes recent advances showing how repurposed agents reshape host immune responses, emphasizing mechanistic pathways in immune cells and the role of macrophages, T-cell immune checkpoint targets, and other immune populations. It surveys candidates reaching clinical stages across cancers, evaluates their effects on innate and adaptive responses, and discusses key obstacles limiting clinical translation.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages16

Reading Time40 min

AccessFree to download

Introduction

Drug repurposing strategies for cancer immunomodulation

Mechanistic pathways in immune cells

Macrophages and T-cell immune checkpoints

Clinical translation and challenges

TYPE Review PUBLISHED 20 March 2026 DOI 10.3389/fonc.2026.1763769 OPEN ACCESS EDITED BY Yuanliang Yan, Central South University, China REVIEWED BY Xiaolin Wu, The Afﬁliated Hospital of Qingdao University, China Keval Raval, Charotar University of Science and Technology (CHARUSAT), India *CORRESPONDENCE Jonaid Ahmad Malik [junaidpsst@gmail.com](junaidpsst@gmail.com) †PRESENT ADDRESS Jonaid Ahmad Malik, Department of Medical Microbiology, Cell Biology and immunology, Southern Illinois University (SIU) School of Medicine, Springﬁeld, IL, United States RECEIVED 09 December 2025 REVISED 28 February 2026 ACCEPTED 03 March 2026 PUBLISHED 20 March 2026 CITATION Malik JA, Talkhan H, Fatima F and Hani U (2026) Recent advancesin drug repurposing for cancer immunomodulation emerging strategies, mechanistic insights, and clinical translation. Front. Oncol. 16:1763769 . doi: 10.3389/fonc.2026.1763769 COPYRIGHT © 2026 Malik, Talkhan, Fatima and Hani. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Recent advances in drug repurposing for cancer immunomodulation emerging strategies, mechanistic insights, and clinical translation Jonaid Ahmad Malik 1*†, Hend Talkhan 2, Farhat Fatima 3 and Umme Hani 4 1 Department of Biomedical Engineering, Indian Institute of Technology, Ropar, India, 2Clinical Pharmacy Department, College of Pharmacy, King Khalid University, Abha, Saudi Arabia, 3 Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj, Saudi Arabia, 4 Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha, Saudi Arabia Drug repurposing is a signiﬁcant strategy in drug discovery, as it saves substantial amounts of time and money. Drugs already approved for other diseases can be repurposed to target cancer. Cancer remains one of the most fatal diseases, and it still does not have a cure. Developing new drug molecules and advancing them from preclinical to clinical stages can take many years, whereas drug repurposing offers a faster alternative. Many repurposed drugs have already progressed to clinical trials. This paper highlights recent advances in how FDA-approved drugs modulate the immune system to enhance host-based immune responses against cancer, and describes the mechanistic pathways through which these drugs acton immune cells. This paper also discusses how targeting macrophages, immune checkpoints on T-Cells, and other immune cell populations can strengthen immunotherapy. In addition, the paper reviews drugs that have advanced to clinical stages and are showing promising results across different cancers, as well as the challenges associated with clinical translation. This paper outlines how drug re purposing can inﬂuence the immune system within the context of cancer chemotherapy. KEYWORDS cancer, drug repurposing, immunomodulation, immunotherapy, oncology Frontiers in Oncology 01 [frontiersin.org](frontiersin.org) Malik et al. 10.3389/fonc.2026.1763769 GRAPHICAL ABSTRACT Drug repurposing for cancer immunomodulation. FDA-approved drugs screened for potential anticancer and immunomodulatory effects. In the preclinical stage, these compounds undergo in vitro testing to evaluate their impact on cancer cells and their modulation of the immune system, followed by in vivo studies in animal models to assess therapeutic efﬁcacy and immune system engagement. The most promising candidates advance to clinical trials, where their ability to modulate innate and adaptive immune responses, including antigen presentat

FAQs

What is the main purpose of drug repurposing in cancer treatment?

Drug repurposing reuses already approved drugs to target cancer, speeding development compared with creating new molecules and moving faster toward clinical evaluation.

How do repurposed drugs enhance antitumor immunity?

They modulate the immune system by acting on immune cells and pathways, including mechanisms related to innate and adaptive responses, immune cell activation, cytokine release, and T-cell functions.

What are the key challenges in translating repurposed drugs into clinical use?

Clinical translation faces hurdles such as funding, intellectual property and regulatory development considerations, along with resistance mechanisms that reduce or limit therapeutic benefit.

Sep 22, 2026

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