In an effort to thrive, cancer cells are able change their epigenetic makeup in order to become resistant to drugs and other forms of treatment, a team of scientists from Singapore has found.
In a study published by Nature Communications on Nov 22, the team from the Agency for Science, Technology and Research’s (A*STAR) Genome Institute of Singapore (GIS) also said they found a new approach to treating cancer by targeting the evolution of cancer cells.
This approach prevents or delays the progression of cancer into treatment-resistant/metastatic disease, the institute said in a press release.
In their study, the scientists discovered that cancer cells constantly evolve under the selection pressure of standard-of-care drugs.
Survival strategies adopted by tumours include “playing dead” by turning dormant and activating resistant or metastasis-associated genes.
“Greater understanding of these mechanisms provides opportunities to target these processes that will help to prevent or delay the spread of cancer,” GIS said.
Traditionally, cancer treatment has primarily focused on the complete elimination of cancer cells through high doses of chemotherapy. But this is difficult when cancer cells begin to adapt to survive.
Using single-cell genomics and patient-derived primary cell (PDPC) models to identify the different modes that cause cancer cells to become resistant or metastatic, the scientists observed that in some patients, cancer cells kept multiplying even when treated with high drug doses.
The theory is that these cells were switching their stem cell factors upon treatment to make themselves drug-resistant.
“The cancer cells behave like chameleons, altering their gene expression and cell behaviour to overcome drug treatment. A comprehensive understanding of tumour evolution and our ability to predict cancer’s next evolutionary move can serve as a way forward to manage therapy resistance in the clinic,” said Dr Ankur Sharma, first author of the study and research associate at GIS.
Dr Ramanuj DasGupta, senior author of the study and group leader at GIS, added: “Like a game of whack-a-mole, cancer cells have a long history of finding alternative routes to evade treatment. By targeting the tumour evolution itself, we aim to prevent or at least delay its progression, and at the same time, avoid the harsh effects of excessive treatment.”
The report also identified the BRD4 gene as a key molecule for resistance. Resistant cells were then treated with JQ1, a drug known to block BRD4 activity, resulting in a reverse or delay of drug-resistance in tumour cells.
- A*STAR’s Genome Institute of Singapore
Medical director at National Cancer Centre Singapore (NCCS), Professor William Hwang, said the findings can help medical practitioners identify patients with cancer who are at the highest risk of having treatment-resistant relapse. Better treatment options may then be offered when a patient suffers a relapse.
Prof Hwang added that NCCS is looking to translate the findings into clinical practice in the near future.