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. 2022 Mar 18;14(6):1548.
doi: 10.3390/cancers14061548.

Stem Cell Theory of Cancer: Implications for Drug Resistance and Chemosensitivity in Cancer Care

Shi-Ming Tu  1 , Charles C Guo  2 , Diana S-L Chow  3 , Niki M Zacharias  4
Affiliations

Stem Cell Theory of Cancer: Implications for Drug Resistance and Chemosensitivity in Cancer Care

Shi-Ming Tu et al. Cancers (Basel). .

Abstract

When it concerns cancer care and cancer therapy, drug resistance is more than an obstacle to successful treatment; it is a major cause of frustration in our attempts to optimize drug development versus therapy development. Importantly, overcoming the challenges of drug resistance may provide invaluable clues about the origin and nature of cancer. From this perspective, we discuss how chemoresistance and chemosensitivity in cancer therapy could be directly linked to the stem cell origin of cancer. A stem cell theory of cancer stipulates that both normal stem cells and cancer stem cells are similarly endowed with robust efflux pumps, potent antiapoptotic mechanisms, redundant DNA repair systems, and abundant antioxidation reserves. Cancer stem cells, like their normal stem cell counterparts, are equipped with the same drug resistance phenotypes (e.g., ABC transporters, anti-apoptotic pathways, and DNA repair mechanisms). Drug resistance, like other cancer hallmarks (e.g., tumor heterogeneity and cancer dormancy), could be intrinsically ingrained and innately embedded within malignancy. We elaborate that cellular context and the microenvironment may attenuate the effects of cancer treatments. We examine the role of circadian rhythms and the value of chronotherapy to maximize efficacy and minimize toxicity. We propose that a stem cell theory of drug resistance and drug sensitivity will ultimately empower us to enhance drug development and enable us to improve therapy development in patient care.

Keywords: cancer stem cells; chemosensitivity; chronotherapy; circadian rhythm; clonal origin; drug development; drug resistance; therapy development; unified theory.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the writing of the manuscript or in the decision to publish the results.

Figures

Figure 1
Figure 1
Stem cell origin of drug resistance in cancer. According to Greek mythology, Karkinos (a crab) is the symbol of cancer. Illustration by Benjamin Tu.
Figure 2
Figure 2
Stem cell origin and a unified theory of cancer: biological processes and clinical implications. Illustration by Benjamin Tu.
See this image and copyright information in PMC

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