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The Dual Role of Natural Peptides in Cancer Therapy: Anticancer and Immunomodulatory Perspectives

Avetis Tsaturyan1,2, Heghine Hakobyan1, Kristina Hovsepyan1, Anna Mkrtchyan1,2, Tatevik Sargsyan1,2,*, Raffaele Pastore3, Germano Guerra3, Giovanni N. Roviello4,*
1 Scientific and Production Center ‘Armbiotechnology’ NAS RA, 14 Gyurjyan Str., Yerevan, Armenia
2 Institute of Pharmacy, Yerevan State University, 1 Alex Manoogian Str., Yerevan, Armenia
3 Department of Medicine and Health Sciences ‘Vincenzo Tiberio’, University of Molise, Via F. De Santis, Campobasso, Italy
4 Institute of Biostructures and Bioimaging (IBB) of the Italian National Council for Research (CNR), Area di Ricerca site and Headquarters, Via Pietro Castellino 111, Naples, Italy
* Corresponding Author: Tatevik Sargsyan. Email: email; Giovanni N. Roviello. Email: email
(This article belongs to the Special Issue: Overcoming Drug Resistance in Cancer: Strategies and Natural Compound-Based Therapeutics)

Oncology Research https://doi.org/10.32604/or.2026.078405

Received 30 December 2025; Accepted 04 March 2026; Published online 10 April 2026

Abstract

Cancer is regarded as one of the leading causes of death worldwide, despite the progress of traditional therapies. Chemotherapy, radiotherapy, and surgery are often accompanied by significant side effects and the development of drug resistance contributes to making the fight against cancer even more challenging, which clearly highlights the urgent need to develop new therapeutic molecular approaches. In this context, natural peptides were introduced into the pharmaceutical market in the last decade and have replenished the ranks of effective anticancer agents due to their structural diversity, biocompatibility, and ability to selectively target tumor cells. Natural peptides play a dual role, directly inhibiting tumor growth and proliferation by inhibiting angiogenesis and, conversely, exhibiting an immunomodulatory effect by enhancing the activation of T lymphocytes and natural killer cells and positively altering the tumor microenvironment (TME). The aim of this work is to critically evaluate the available literature on the anticancer and immunomodulatory activities of natural peptides and their potential use, both as monotherapy and in combination therapy, with particular attention given to issues of stability, bioavailability, and scalability of production. As highlighted throughout this review, a promising area is the integration of natural peptides with their synthetic derivatives and combining them with modern approaches such as nanotechnology and personalized medicine, which opens new avenues in cancer treatment.

Keywords

Natural peptides; anticancer therapy; immunomodulation; tumor microenvironment; angiogenesis inhibition; drug resistance; nanotechnology; personalized medicine

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