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

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Neoplasms*/drug therapy ; Neoplasms*/metabolism ; Neoplasms*/pathology ; Cell Communication*; Humans ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Tumor Microenvironment/drug effects ; Animals ; Immunological Synapses/metabolism

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.

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0903-2 Moscow Government

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

0 (Antineoplastic Agents)

Date Created: 20241016 Date Completed: 20241016 Latest Revision: 20241019

20241019

PMC11476449

10.3390/ijms251910454

39408784