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The Unholy Trinity- Cancer cell plasticity, drug resistance and therapeutic opportunities
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  • Namrata Chatterjee,
  • Bhavana Pulipaka,
  • Ayalur Raghu Subbalakshmi,
  • Mohit Kumar Jolly,
  • Radhika Nair
Namrata Chatterjee
National Institute of Technology Rourkela
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Bhavana Pulipaka
Ashoka University
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Ayalur Raghu Subbalakshmi
Indian Institute of Science
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Mohit Kumar Jolly
Indian Institute of Science
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Radhika Nair
Rajiv Gandhi Centre for Biotechnology

Corresponding Author:[email protected]

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Cancer cell plasticity is the ability of tumor cells to switch phenotypes and is one of the predominant requisites of cancer cells capable of undergoing metastasis. Cancer cell plasticity is also recognised as one of the major contributors to intra-tumoral heterogeneity, a critical factor underlying the progression of malignant tumors which is known to modify tumor response and induce resistance against various modes of therapy thus posing a barrier to efficient cancer management. Cancer cell plasticity is acquired by the subversion of cell signaling pathways like MAPK, PI3K, STAT3, Wnt, Hedgehog and Notch as well as cellular programs such as epithelial to mesenchymal transition (EMT) and phenotypic plasticity. This complex phenomenon has been studied in many cancer types like pancreatic cancer, colon cancer and breast cancer. Some cancers like breast cancer are known to exhibit a hierarchical organization with cancer stem cells (CSCs) at the pinnacle of the pyramid due to their ability to promote tumorigenesis, metastasis and therapy resistance. CSCs which can undergo phenotypic changes resulting in heterogenous cell populations with differing potential to develop programs necessary for the metastatic process lies at the core of the cancer cell plasticity hypothesis. Our expanding knowledge of this field can lead to the development of more therapeutic strategies that can be used in cancer and other solid tumors that exhibit similar mechanisms of plasticity. This review will explore the current understanding we have of breast cancer on the intrinsic molecular mechanisms of cancer cell plasticity and the resistance to various types of cancer therapy that arise as a result of plasticity. We conclude by exploring the potential novel therapies that specifically target the pathways leading to plasticity and can be leveraged to treat patients living with the disease. Keywords: Cancer cell plasticity, Epithelial to Mesenchymal Transition (EMT), therapy resistance, targeted therapy.
29 Dec 2022Submitted to Computational and Systems Oncology
02 Feb 2023Assigned to Editor
02 Feb 2023Submission Checks Completed
02 Feb 2023Review(s) Completed, Editorial Evaluation Pending
28 Feb 2023Reviewer(s) Assigned
28 Feb 2023Reviewer(s) Assigned
20 May 2023Editorial Decision: Revise Minor
26 Jul 20231st Revision Received
27 Jul 2023Assigned to Editor
27 Jul 2023Submission Checks Completed
27 Jul 2023Review(s) Completed, Editorial Evaluation Pending
27 Jul 2023Editorial Decision: Accept