Three unconventional maxims in the natural selection of cancer cells - Generation of induced tumor-suppressing cells (iTSCs)

Sep 24, 2026

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Induced tumor-suppressing cells (iTSCs) can be generated from both cancer and non-cancer cells. The review summarizes three paradoxical principles governing iTSC action: secretion of tumor-suppressing proteins, their function as a “double-edged” mechanism, and elimination of less-fit cancer cells. The maxims highlight a therapeutic dilemma because inhibitory treatments may stimulate tumor-promoting protein production. The synthesis supports a potential treatment direction using cancer-guided evolutionary-fit iTSCs.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

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Abstract

Natural Selection and Therapeutic Strategy

Cell competition and therapeutic dilemma

Evolution-inspired treatment strategies

Extinction, adaptation, and adaptive therapy

Ivyspring International Publisher InternationalJournal of Biological Sciences 2023; 19(5): 1403-1412. doi: 10.7150/ijbs.79155 Review Three unconventional maxims in the natural selection of cancer cells: Generation of induced tumor-suppressing cells (iTSCs) Kexin Li1,2, Qingji Huo1,2, Bai-Yan Li1, and Hiroki Yokota2,3,4􀀍 1. Department of Pharmacology, School of Pharmacy, Harbin Medical University, Harbin 150081, China 2. Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USA 3. Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, IN 46202, USA 4. Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA 􀀍 Corresponding author: Hiroki Yokota, Ph.D., Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, 723 West Michigan Street, SL220, Indianapolis, IN 46202 USA. Phone: 317-278-5177; Fax: 317-278-2455; Email: [hyokota@iupui.edu. Bai-Yan](hyokota@iupui.edu. Bai-Yan) Li, MD/Ph.D., Department of Pharmacology, School of Pharmacy, Harbin Medical University, \#157 Baojian Road, Harbin 150081, China. Phone/Fax: +86 451-8667-1354; E-mail: [liby@ems.hrbmu.edu.cn](liby@ems.hrbmu.edu.cn) © The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License ([https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/)). See [http://ivyspring.com/terms](http://ivyspring.com/terms) for full terms and conditions. Received: 2022.09.22; Accepted: 2023.02.16; Published: 2023.02.27 Abstract Induced tumor-suppressing cells (iTSCs) can be generated from cancer and non-cancer cells. Here, three paradoxical maxims for the action of iTSCs are reviewed: the secretion of tumor-suppressing proteins, their role as a “double-edged” sword, and the elimination of lesser-fit cancer cells.“Super-fit” cancer cells secrete an array of proteins, most of which contribute to enhancing their growth and removing“lesser-fit” cancer cells. These maxims explain the potential dilemma with therapeutic agents since the inhibitory agents tend to promote the synthesis of tumor-promoting proteins. The maxims suggest the possibility of a novel treatment option using cancer-guided evolutionary-fit iTSCs. Keywords: natural selection, tumor proteome, iTSCs, conditioned medium, protein cocktail Natural Selection and Therapeutic Strategy Cell competition eliminates cells that are viable but less fit than the surrounding cells [1] . Therapeutically, cell competition could play a beneficial role by removing damaged cells and eliminating cells carrying oncogenic mutations (reviewed by [2], [3]) . In most cancer treatments, however, cell competition is a difficult problem to address since it promotes the expansion of oncogenic clones and the development of resistance to treatments [4] . In their review, Parker et al. suggest that cancer cells acquire a super competent phenotype by steadily accumulating genomic aberrations that promote the death of surrounding healthy cells to initiate and promote oncogenesis [5] . As asked by Bowling et al. [1], a central question herein is whether it is possible to harness cell competition for the benefit of treating primary and advanced metastatic cancer. If“yes”, what therapeutic strategy should be developed? By citing Dobzhansky’s remark on evolution,“nothing in biology makes sense except in the light of evolution,” Greaves stated that the therapeutic resistance of advanced cancers is a consequence of a complex, dynamic, and adaptive environment, underpinned by genetic diversity and epigenetic plasticity [6] . He proposed a three-step strategy to control cancer, including (1) stopping it before it gets started by avoiding cigarettes and UV, and maintaining healthy diets and physical activities, (2) detecting it early and removing it when localized by

FAQs

What are induced tumor-suppressing cells (iTSCs) and how can they be generated?

iTSCs can be generated from cancer cells and non-cancer cells. The review discusses how their function can be shaped through these origins.

What are the three paradoxical maxims reviewed for iTSCs?

The review highlights three maxims: iTSCs secrete tumor-suppressing proteins, they act as a “double-edged” mechanism, and they eliminate less-fit cancer cells.

Why can therapeutic inhibition create a dilemma described in the review?

The inhibitory agents that block tumors can also promote synthesis of tumor-promoting proteins, complicating treatment outcomes and evolutionary responses.

Sep 24, 2026

Uploaded by Eliana