Interferon-Based Therapeutics in Cancer Therapy - Past, Present, and Future

Sep 24, 2026

Uploaded by nayy☆

Interferons (IFNs) are multifunctional immunostimulatory proteins central to innate and adaptive immunity, driving early antiviral responses while also exhibiting immunomodulatory and antiproliferative activity. Because early IFN use in oncology was constrained by frequent severe adverse effects, this review focuses on recombinant IFNs in anticancer therapy and on emerging IFN-based gene therapy strategies. Emphasis is placed on safety, therapeutic efficacy, interferon types, and clinical roles across combined cancer treatments and select rare diseases.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages30

Reading Time1 h 16 min

AccessFree to download

Abstract

Keywords

1. Introduction

2. The Innate Antiviral Response. Signaling Pathways for Type I IFN Production

Review Interferon-Based Therapeutics in Cancer Therapy: Past, Present, and Future Kristina Vorona , Anastasia Ryapolova , Olesya Sokolova , Alexander Karabelsky , Roman Ivanov , Vasiliy Reshetnikov *,† and Ekaterina Minskaia *,† Academic Editor: Elena Levantini Received: 13 November 2025 Revised: 28 November 2025 Accepted: 28 November 2025 Published: 2 December 2025 Citation: Vorona, K.; Ryapolova, A.; Sokolova, O.; Karabelsky, A.; Ivanov, R.; Reshetnikov, V.; Minskaia, E. Interferon-Based Therapeutics in Cancer Therapy: Past, Present, and Future. Int. J. Mol. Sci. 2025, 26, 11679 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms262311679 Copyright: © 2025 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://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) . Translational Medicine Research Center, Sirius University of Science and Technology, 1 Olympic Avenue, 354340 Sochi, Russia * Correspondence: [reshetnikov.vv@talantiuspeh.ru](reshetnikov.vv@talantiuspeh.ru) (V.R.); [minskaya.es@talantiuspeh.ru](minskaya.es@talantiuspeh.ru) (E.M.)† These authors contributed equally to this work. Abstract Interferons (IFNs) are well-known immunostimulants involved in both innate and adaptive immune responses. These multifunctional proteins mediate an early antiviral response and have pronounced immunomodulatory and antiproliferative properties. Due to their potency, IFNs have been used not only in the treatment of viral infections but also various other diseases. However, the use of IFNs in antitumor therapy has been limited by the frequent severe side effects, which reduced their appeal for the treatment of cancer. In this review, we focused on current data on recombinant IFNs used for anticancer therapy, as well as the development of promising IFN-based gene therapy approaches, with a focus on their safety and therapeutic efficacy. We also highlighted various types of IFNs and their application niches in the treatment of not only cancers in combination therapy but also of certain rare diseases. Taken together, this review improves our understanding of the existing IFN applications in cancer therapy, the disadvantages of using IFNs, and possible approaches for their improvement. Keywords: interferon; IFN; interferon type; anti-cancer therapy; antitumor therapy 1. Introduction Cancer is a disease caused by mutations or epigenetic changes in the body’s cells, which leads to their uncontrolled growth and division, followed by the formation of a tumor and possible metastasis [1] . Despite the intensive development of new approaches in cancer therapy, including immune checkpoint inhibitors, bispecific T-cell engagers (BiTE), oncovirotherapy, and chimeric antigen receptor T-cell therapy (CAR-T), the number of cancer patients is steadily increasing [2] . According to global cancer statistics, in 2022, almost 20 million people had cancer, and about 10 million died from it [3] . The forecasts predicting the number of new cases are concerning: 35 million people with cancer are expected to be diagnosed by 2050 [3] . Interferons (IFNs) occupy one of the central places among well-known anticancer agents. After their discovery more than 50 years ago, the FDA approved the first recombinant IFNa2b (Intron A® )-based drug in 1986 (almost 30 years ago), which was used for the treatment of melanoma, kidney cancer, follicular lymphoma, and various types of leukemia [4] . IFNs are involved in antiviral immunity and the fight against cancer cells [5,6] . Type I interferons (IFN-I) include 13 subtypes of IFN-α, as well as IFN-β, IFN-ω, IFN-ε, and IFN-κ, while IFN-γ is a type II interferon. Therapies based on IFN-α and IFN-γ have a pronounced antitumor effect on different types of

FAQs

Why are interferons important in cancer therapy?

Interferons participate in antiviral immunity and can exert antitumor effects. They also show immunomodulatory and antiproliferative properties relevant to cancer treatment.

What limited the use of interferons in antitumor therapy?

Frequent severe side effects reduced their appeal. Reported problems include short half-life, low efficacy, numerous often intolerable side effects, and off-target effects from interferon receptors on many cell types.

What does the review cover regarding future directions?

It analyzes approved IFN-based drugs, discusses promising results from IFN-based clinical trials, and highlights potential improvement approaches. It also focuses on IFN-based gene therapy approaches with attention to safety and efficacy.

Sep 24, 2026

Uploaded by nayy☆