If you were to look inside a cancer tumour, you’d notice that not all cells within it look the same. In fact, over the past decade researchers have shown that tumours contain several different types of cells, each with different functions and unique characteristics.
Intra-tumour heterogeneity poses a big problem for current cancer therapies, which are not always designed to kill all the cell-types that cohabitate within a tumour. This can lead to serious complications: if certain types of cells survive treatment, then there’s a good chance the tumour might grow back.
One of the major culprits behind cancer relapse is a family of cells known as cancer stem-like cells (CSLCs). These cells, which can be found in tumours across different types of cancer, are biologically different than their counterparts and often survive therapeutic assault. Add to this the fact that they have unique self-renewing abilities that allow them to proliferate after therapy, and you can begin to understand why a new discovery by a team of scientists based in Nova Scotia searching for new ways to target CSLCs is so important.
In a study published in Autophagy (May 2019), the team led by Dr. Shashi Gujar, head of the laboratory for cancer metabolism, cell biology and immunotherapies at Dalhousie University, revealed that silencing TP73/p73, a protein that has long been understood to have tumour-suppressing qualities, could disrupt metabolic pathways in CSLCs, abrogating their self-renewal potential.
“We found that Tp73 is required by the stem-like cancer cells to maintain their growth and stemness features, and that silencing TP73 drastically suppresses these characteristics,” said Dr. Gujar. “Hence, p73 has emerged as a potential anti-tumour target.”
This study used tumour cells surgically resected from brain tumour patients, which were facilitated by a Terry Fox New Frontiers Program Project Grant led by Dr. Sheila Singh (McMaster University). According to Dr. Gujar, this type of pan-Canadian collaboration between distant and seemingly unrelated research teams is key to making important discoveries that will have an impact on cancer patients.
“This organic cancer research collaboration celebrates the true spirit of cross-Canadian collaborative research as envisioned by TFRI,” said Dr. Gujar. “And this type of precision medicine approach will allow for the development of strategies that can eventually eradicate all cancer cells and promote long-term cancer-free health.”
Regulation of the proline regulatory axis and autophagy modulates stemness in TP73/p73 deficient cancer stem-like cells
Tanveer Sharif, Emma Martell, Cathleen Day, Sheila K. Singh and Shashi Gujar
This study was partially funded by a Terry Fox New Frontiers Program Project Grant in Targeting clonal heterogeneity in treatment-refractory glioblastoma with novel and empiric immunotherapies