Tumor Cell Communications as Promising Supramolecular Targets for Cancer Chemotherapy: A Possible Strategy

Sep 21, 2026

Uploaded by Rowan

Fifty-two years after President Nixon launched the “War on Cancer,” chemotherapy, radiation, hormonal and targeted therapies have not met expectations. A literature-based strategy is proposed to chemically target connections between cancer cells and their microenvironment, especially cancer–stromal synapses. Immunological-synapse ligand–receptor clusters coordinate intercellular signaling, and disrupting these synapses may collapse diverse tumors. Clustered components also enable safer, more precise treatment via targeted crosslinking and cleavable cell-permeable toxic agents. The approach aims to be universal, simple, and cost-efficient, with reduced likelihood of resistance compared with single-target drugs.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages20

Reading Time50 min

AccessFree to download

Abstract

1. Introduction—Chemotherapy: Fame and Failure

Review Tumor Cell Communications as Promising Supramolecular Targets for Cancer Chemotherapy: A Possible Strategy Irina Alekseenko 1,2, Lyudmila Zhukova 3, Liya Kondratyeva 1,2, *, Anton Buzdin 1,4,5, Igor Chernov 1 and Eugene Sverdlov 2, * Citation: Alekseenko, I.; Zhukova, L.; Kondratyeva, L.; Buzdin, A.; Chernov, I.; Sverdlov, E. Tumor Cell Communications as Promising Supramolecular Targets for Cancer Chemotherapy: A Possible Strategy. Int. J. Mol. Sci. 2024, 25, 10454 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms251910454 Academic Editor: Mohamed Hassan Received: 5 September 2024 Revised: 25 September 2024 Accepted: 26 September 2024 Published: 27 September 2024 Copyright: © 2024 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/)) . 1 Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 117997 Moscow, Russia; [irina.alekseenko@gmail.com](irina.alekseenko@gmail.com) (I.A.); [buzdin@oncobox.com](buzdin@oncobox.com) (A.B.); [igor.palich@gmail.com](igor.palich@gmail.com) (I.C.) 2 National Research Center “Kurchatov Institute”, 123182 Moscow, Russia 3 Department of Oncology, SBIH “Moscow Clinical Scientific and Practical Center Named After A.S. Loginov”DHM, 111123 Moscow, Russia; [zhukova.lyudmila@rambler.ru](zhukova.lyudmila@rambler.ru) 4 World-Class Research Center “Digital Biodesign and Personalized Healthcare”, Sechenov First Moscow State Medical University, 119992 Moscow, Russia 5 Oncobox LLC, 121205 Moscow, Russia * Correspondence: [liakondratyeva@yandex.ru](liakondratyeva@yandex.ru) (L.K.); [edsverd@gmail.com](edsverd@gmail.com) (E.S.) Abstract: Fifty-two years have passed since President Nixon launched the “War on Cancer”. Despite unparalleled efforts and funds allocated worldwide, the outlined goals were not achieved because cancer treatment approaches such as chemotherapy, radiation therapy, hormonal and targeted therapies have not fully met the expectations. Based on the recent literature, a new direction in cancer therapy can be proposed which targets connections between cancer cells and their microenvironment by chemical means. Cancer–stromal synapses such as immunological synapses between cancer and immune cells provide an attractive target for this approach. Such synapses form ligand–receptor clusters on the interface of the interacting cells. They share a common property of involving intercellular clusters of spatially proximate and cooperatively acting proteins. Synapses provide the space for the focused intercellular signaling molecules exchange. Thus, the disassembly of cancer– stromal synapses may potentially cause the collapse of various tumors. Additionally, the clustered arrangement of synapse components offers opportunities to enhance treatment safety and precision by using targeted crosslinking chemical agents which may inactivate cancer synapses even in reduced concentrations. Furthermore, attaching a cleavable cell-permeable toxic agent(s) to a crosslinker may further enhance the anti-cancer effect of such therapeutics. The highlighted approach promises tobe universal, relatively simple and cost-efficient. We also hope that, unlike chemotherapeutic and immune drugs that interact with a single target, by using supramolecular large clusters that include many different components as a target, the emergence of a resistance characteristic of chemo-and immunotherapy is extremely unlikely. Keywords: cancer; tumor microenvironment; cell interaction; immunological synapse; crosslinking agents; next-generation chemotherapy; targeted therapeutics 1. Introduction—Chemotherapy: Fame and Failure The year 2023 ma

FAQs

Why does the article propose a new direction in cancer therapy?

Despite large worldwide efforts since the “War on Cancer,” the promised goals were not achieved because major treatment modalities have not fully met expectations. The article suggests targeting cancer–microenvironment connections as a new chemical strategy.

What is the main therapeutic concept involving cancer–stromal synapses?

Cancer–stromal synapses, including immunological synapses between cancer and immune cells, form ligand–receptor clusters that organize intercellular signaling. The article proposes that disassembling these synapses may cause tumors to collapse.

How could clustered synapse components improve treatment safety and resistance?

The article highlights that clustered arrangements enable targeted crosslinking chemical agents to inactivate cancer synapses at reduced concentrations, potentially improving safety and precision. By using supramolecular large clusters with many components as the target, the emergence of chemo- and immunotherapy resistance is considered extremely unlikely.

Sep 21, 2026

Uploaded by Rowan