27th June 2017

Overcoming drug resistance in cancer by unmasking cell identity theft

‘Cancer cells escaped drug treatment and lived ever after under a different cell identity’ is the sad headline for about 8 million cancer patients worldwide1. Indeed, resistance to treatment occurs when tumours that have been previously responding to anti-cancer therapies suddenly begin to grow again. In other words, cancer cells can develop the ability to resist the effects of treatment. One major reason for this phenomenon is that cancer cells can escape treatment by adopting a new and more robust cellular identity. This new identity enables cancer cells to reproduce and generate further cancer cells, which in turn fuels tumour regrowth. Because this cellular identity resembles that of stem cells, which normally provide a pool of new cells that the body uses to restock damaged or old cells, these cancer cells are called ‘cancer stem cells’.

A number of studies have shown that exposure to conventional anti-cancer treatment can promote cancer cells to become cancer stem cells, which increases their chances of survival. Such treatments comprise conventional chemotherapy, targeted therapies, and radiation therapy2,3,4,5. Specifically, exposure to these treatments has been shown to activate proteins that regulate the growth of cells, preventing cell death3. Cancer stem cells also have chemical changes in their DNA, which carries the genetic instructions used in the growth, development, and functioning of cells2. Furthermore, cellular components that promote the regeneration of stem cells have been found in cancer stem cells too4,5. These findings are significant, as they highlight the amount of change that cancer cells undertake to turn into cancer stem cells.

However, scientists are hopeful in their quest for therapies that will prevent cancer cells from acquiring cancer stem cell properties. They are currently targeting specific factors called cytokines which are thought to promote a favourable environment for the formation of cancer stem cells6. They are also trying to reverse the chemical changes in the DNA of cancer stem cells. These new therapies, when used in conjunction with conventional treatments, are showing promise.

References
1) American Cancer Society. Global Cancer Facts & Figures. https://www.cancer.org/research/cancer-facts-statistics/global.html (accessed June 2017). 
2) Sharma SV, et al. Cell 2010; 141: 69-80.
3) Goldman A, et al. Nat Commun 2015; 6: 6139.
4) Ghisolfi L, et al. PLoS One 2012; 7: 1-11.
5) Hu X, et al. Cell Cycle 2012; 11: 2691-8.
6) Doherty MR, et al. Cancers (Basel) 2016; 8: 1-13.