Researchers have uncovered a mechanism that makes cancer cells immortal and identified potential treatment options that could help kill aggressive cells.
The normal cells that make up our body divide throughout our lives to ensure our bodies can keep on functioning. As they divide, protective structures found at the ends of chromosomes, called telomeres, get shorter and shorter until the cell eventually stops dividing.
Cancer cells, on the other hand, have a way of cheating this natural life-cycle. By repairing the chromosome ends, cancer cells can make themselves immortal, enabling them to keep on dividing and allowing tumours to grow and spread.
Associate Professor Hilda Pickett from the Children’s Medical Research Institute has been studying the way some of the most aggressive cancers cheat death – a process they call ‘alternative lengthening of telomeres’ or ALT. Put simply, through ALT, a cancer cell ‘copies and pastes’ the protective telomere from chromosomes with long telomeres onto those with short telomeres, rescuing the cell from what should be its natural death.
About 40% of soft-tissue cancers (including osteosarcoma, and cancers that originate in fat cells and blood vessels), as well as 10% of solid cancers (such as breast, ovarian and prostate) activate the ALT process to survive. There are currently no specific treatments for ALT cancers. People with this type of cancer experience poorer treatment outcomes and have a higher risk of death because ALT cancers are often resistant to current therapies.
Associate Professor Pickett and her team have identified a protein, called FANCM, that is essential to the ALT process. To test whether manipulating this protein would impact the survival of ALT cancer cells, the team joined forces with Associate Professor Andrew Deans at St Vincent’s Institute. Together they discovered that by disrupting the function of FANCM, they could put the cancer under so much stress that it stopped proliferating.
Having identified a promising target, the research teams set out to find agents or drugs that could inhibit the protein. They found that FANCM could be inhibited with specific peptides, and an experimental drug called PIP-199.
The next step is to study the effectiveness of these peptides and PIP-199, and improve drug potency and delivery, prior to pre-clinical testing and eventually clinical trials. If this approach proves to be successful, it could be life-changing and life-saving for children and other people with these cancers.
Associate Professor Hilda Pickett Children’s Medical Research Institute