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Review

Phenotypic Plasticity and Cancer: A System Biology Perspective

by
Ayalur Raghu Subbalakshmi
1,
Sravani Ramisetty
1,
Atish Mohanty
1,
Siddhika Pareek
1,
Dana Do
1,
Sagun Shrestha
2,
Ajaz Khan
3,
Neel Talwar
4,
Tingting Tan
5,
Priya Vishnubhotla
6,
Sharad S. Singhal
1,
Ravi Salgia
1,* and
Prakash Kulkarni
1,7,*
1
Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA 91010, USA
2
Department of Medical Oncology and Therapeutics Research, City of Hope Phoenix, Goodyear, AZ 85338, USA
3
Department of Medical Oncology and Therapeutics Research, City of Hope Chicago, Zion, IL 60099, USA
4
Department of Medical Oncology and Therapeutics Research, City of Hope San Bernardino Road, Upland, CA 91786, USA
5
Department of Medical Oncology and Therapeutics Research, City of Hope Avocado Avenue, Newport Beach, CA 92660, USA
6
Department of Medical Oncology and Therapeutics Research, City of Hope Atlanta, Newnan, GA 30265, USA
7
Department of Systems Biology, City of Hope National Medical Center, Duarte, CA 91010, USA
*
Authors to whom correspondence should be addressed.
J. Clin. Med. 2024, 13(15), 4302; https://doi.org/10.3390/jcm13154302
Submission received: 20 May 2024 / Revised: 1 July 2024 / Accepted: 18 July 2024 / Published: 23 July 2024
(This article belongs to the Section Clinical Laboratory Medicine)
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Abstract

Epithelial-to-mesenchymal transition (EMT) is a major axis of phenotypic plasticity not only in diseased conditions such as cancer metastasis and fibrosis but also during normal development and wound healing. Yet-another important axis of plasticity with metastatic implications includes the cancer stem cell (CSCs) and non-CSC transitions. However, in both processes, epithelial (E) and mesenchymal (M) phenotypes are not merely binary states. Cancer cells acquire a spectrum of phenotypes with traits, properties, and markers of both E and M phenotypes, giving rise to intermediary hybrid (E/M) phenotypes. E/M cells play an important role in tumor initiation, metastasis, and disease progression in multiple cancers. Furthermore, the hybrid phenotypes also play a major role in causing therapeutic resistance in cancer. Here, we discuss how a systems biology perspective on the problem, which is implicit in the ‘Team Medicine’ approach outlined in the theme of this Special Issue of The Journal of Clinical Medicine and includes an interdisciplinary team of experts, is more likely to shed new light on EMT in cancer and help us to identify novel therapeutics and strategies to target phenotypic plasticity in cancer.
Keywords: plasticity; epithelial mesenchymal transition; hybrid E/M cells; circulating tumor cells plasticity; epithelial mesenchymal transition; hybrid E/M cells; circulating tumor cells

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MDPI and ACS Style

Subbalakshmi, A.R.; Ramisetty, S.; Mohanty, A.; Pareek, S.; Do, D.; Shrestha, S.; Khan, A.; Talwar, N.; Tan, T.; Vishnubhotla, P.; et al. Phenotypic Plasticity and Cancer: A System Biology Perspective. J. Clin. Med. 2024, 13, 4302. https://doi.org/10.3390/jcm13154302

AMA Style

Subbalakshmi AR, Ramisetty S, Mohanty A, Pareek S, Do D, Shrestha S, Khan A, Talwar N, Tan T, Vishnubhotla P, et al. Phenotypic Plasticity and Cancer: A System Biology Perspective. Journal of Clinical Medicine. 2024; 13(15):4302. https://doi.org/10.3390/jcm13154302

Chicago/Turabian Style

Subbalakshmi, Ayalur Raghu, Sravani Ramisetty, Atish Mohanty, Siddhika Pareek, Dana Do, Sagun Shrestha, Ajaz Khan, Neel Talwar, Tingting Tan, Priya Vishnubhotla, and et al. 2024. "Phenotypic Plasticity and Cancer: A System Biology Perspective" Journal of Clinical Medicine 13, no. 15: 4302. https://doi.org/10.3390/jcm13154302

APA Style

Subbalakshmi, A. R., Ramisetty, S., Mohanty, A., Pareek, S., Do, D., Shrestha, S., Khan, A., Talwar, N., Tan, T., Vishnubhotla, P., Singhal, S. S., Salgia, R., & Kulkarni, P. (2024). Phenotypic Plasticity and Cancer: A System Biology Perspective. Journal of Clinical Medicine, 13(15), 4302. https://doi.org/10.3390/jcm13154302

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