Two new potential cancer therapies identified

An Australian study undertaken by St Vincent’s Institute of Medical Research (SVI) in Melbourne and Children’s Medical Research Institute in Sydney, has uncovered a mechanism of cancer survival and identified not one, but two, potential treatment options that could help kill aggressive cells that lead to both rare children’s’ cancers and common cancers.

“Cells divide throughout our lives to ensure our bodies can keep on functioning; but as they divide, the structures found at the ends of chromosomes called telomeres, get shorter and shorter, until the cell eventually dies,” said senior author, Associate Professor Hilda Pickett from CMRI in Sydney.

Cancer cells find a way around this limitation using one of two approaches to repair the chromosome: 1) the enzyme telomerase is activated to add new telomeres to the DNA ends or 2) through a process called “alternative lengthening of telomeres”, or ALT, which copy/pastes telomere DNA from chromosomes with long telomeres onto those with short telomeres.

“About 40% of soft-tissue cancers including osteosarcoma (bone cancer), liposarcoma (a cancer originating in fat cells), and angiosarcoma (blood vessel cancer), as well as 10% of other carcincoma cancer types, such as breast, ovarian and prostate, occur when the ALT process is activated and the cells become ‘immortal’ and cancerous”, said co-first author Dr Julienne O’Rourke from SVI in Melbourne. “There are currently no specific therapies for ALT-positive sarcomas. People with this type of cancer have a 50% higher rate of death, as these cancers are more resistant to current treatments.”

Associate Professor Pickett said they’d been studying the mechanics of ALT cancers for many years when they identified a protein that is essential for ALT cell viability. The research involved collaboration with Associate Professor Andrew Deans at St Vincent’s Institute in Melbourne to demonstrate that depletion of FANCM was specifically toxic to ALT cancer cells. Together they discovered that by disrupting the function of FANCM, they could put the cancer under so much stress that it stopped proliferating.

Another study by SVI undertaken with international collaborators in Portugal and Switzerland2, also revealed that ALT-positive cancer cells die when FANCM is deleted.

“Both studies, published today in Nature Communications, found that absence of the FANCM enzyme “hijacks” the ALT process and causes very specific cancer cell killing. The FANCM enzyme is not essential in normal (non-cancerous) cells,” said co-senior author Associate Professor Andrew Deans from SVI. “This suggests it could be a good target for new drugs that could eliminate cancer cells, without eliminating other healthy cells.”

“Further, we found that FANCM could be inhibited with specific peptides, or an experimental drug called PIP-199.  The next step is to do new studies with these peptides and PIP-199 to get to the stage where we can begin clinical trials,” said Associate Professor Hilda Pickett.

“We’re all excited by the life-changing and life-saving potential for children and other people with these cancers; it’s not every day you make discoveries that could lead to treatments that could save not a few, but many, precious lives.”

The original article, featured on the St Vincent’s Medical Research website, can be found here.