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Review

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

1
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 117997 Moscow, Russia
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
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
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2024, 25(19), 10454; https://doi.org/10.3390/ijms251910454
Submission received: 5 September 2024 / Revised: 25 September 2024 / Accepted: 26 September 2024 / Published: 27 September 2024
(This article belongs to the Special Issue Advances and Perspectives in Molecular Tumor Therapy)

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 to be 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 cancer; tumor microenvironment; cell interaction; immunological synapse; crosslinking agents; next-generation chemotherapy; targeted therapeutics

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MDPI and ACS Style

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/ijms251910454

AMA Style

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. International Journal of Molecular Sciences. 2024; 25(19):10454. https://doi.org/10.3390/ijms251910454

Chicago/Turabian Style

Alekseenko, Irina, Lyudmila Zhukova, Liya Kondratyeva, Anton Buzdin, Igor Chernov, and Eugene Sverdlov. 2024. "Tumor Cell Communications as Promising Supramolecular Targets for Cancer Chemotherapy: A Possible Strategy" International Journal of Molecular Sciences 25, no. 19: 10454. https://doi.org/10.3390/ijms251910454

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