A team of Walter and Eliza Hall Institute (WEHI) researchers in Melbourne has worked out how a new class of anticancer drugs kills cancer cells. The finding also helps explain how cancer cells may become resistant to treatment.
Dr Zhen Xu, Professor David Huang, Dr Stefan Glaser and colleagues studied a class of anti-cancer drugs called BET inhibitors, which are considered promising new drugs for the treatment of blood cancers such as leukaemia and lymphomas.
BET inhibitors reduce tumour growth by blocking BET proteins, a family of proteins that control whether genes are switched on or off.
Although it has been known that BET inhibitors are effective at halting tumour growth, it has been unclear whether the drugs kill cancer cells outright or merely pause their growth.
Details on programmed cell death revealed
The research team found that when tumours are treated with drugs, some resistant cancer cells can survive and continue to grow, leading to disease relapse. In the process they identified potential ways in which cancer cells may develop resistance to BET inhibitors.
The experiments revealed that BET inhibitors principally act to kill cancer cells through the process of programmed cell death (apoptosis). For BET inhibitors to successfully kill lymphoma and myeloid leukemia cells the presence of a protein called BIM, which brings on apoptosis, was critical.
“We found that when apoptosis was impaired, for instance by loss of BIM, the BET inhibitors were no longer effective,” Dr Xu said.
“This suggests that cancer cells that acquire mutations in genes that drive apoptosis will lose sensitivity to BET inhibitors and thus will be able to survive treatment, leading to disease relapse.”
Dr Glaser said that knowing how BET inhibitors worked could help researchers develop improved strategies for using these drugs to treat cancer.
“Understanding how the drugs work gives us the opportunity to investigate new treatments, for example by using combination therapies, or altering the dosage and timing of treatment to prevent drug resistance from emerging,” Dr Glaser said.
The findings have been published in the journal Leukaemia. The original news post was published on the WEHI website.
The research has been supported by the Australian National Health and Medical Research Council, Cancer Council Victoria, the Leukaemia and Lymphoma Society, the China Scholarship Council, the Australian Cancer Research Foundation and a Victorian Government Operational Infrastructure Support Grant.