The Unholy Trinity- Cancer cell plasticity, drug resistance and
therapeutic opportunities
Abstract
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.