Cancer stem cells could be easier to target following world-first discovery by Australian researchers
December 12, 2014
Children’s Cancer Institute researchers have identified, for the first time, new properties essential to drug-resistant tumour cells that could revolutionise cancer treatment and reduce the side-effects of chemotherapy.
The study was published this month in Blood and is the first to prove that a key cellular signalling mechanism, essential to the survival of cancer stem cells, is quite different to that of normal, healthy stem cells.
The often debilitating side-effects of chemotherapy are caused by cytotoxic drugs that indiscriminately attack rapidly dividing cells – both malignant and healthy – including cells in the bone marrow, digestive tract and hair follicles. Understanding the different components of this mechanism in cancer stem cells will provide the opportunity to develop new therapies that will target these cells, while leaving normal, healthy cells untouched.
A critical protein called β-catenin is a key driver for the survival of cancer stem cells. The β-catenin pathway was identified decades ago, and since then drug companies have tried to target and ‘block’ it to eliminate cancer cells – but because β-catenin is located inside a cell’s nucleus, the delivery of drugs via this pathway was considered impossible.
This study – led by Dr Jenny Wang, leader of Children’s Cancer Institute’s Cancer and Stem Cell Biology group – has uncovered a novel gene known as GPR84, which plays a key part in the β-catenin pathway and sits on the surface of the cancer cell.
“A gene that sits on the surface of a cell is much easier to target,” says Dr Wang, “and in identifying GPR84 as one of the drivers of cancer stem cells, we’re gaining a better understanding of the pathways they rely on to survive.”
Dr Wang’s study focuses solely on acute myeloid leukaemia – a form of acute leukaemia that is much more difficult to treat and has a significantly poorer prognosis than the commonest childhood cancer, acute lymphoblastic leukaemia. However, as the β-catenin pathway is active in a wide variety of cancers and in cancer stem cells including liver, colon, brain and skin, her findings can potentially be applied to a number of cancers in both children and adults.
“Cancer stem cells can be incredibly drug-resistant and a main cause of relapse in patients – so it’s critical we understand how they behave in order to target and eliminate them,” continued Dr Wang. “By uncovering GPR84, we’ve made an important step towards this goal.”
Dr Wang’s study reflects Children’s Cancer Institute’s vision, which is to identify and develop more targeted, effective and less toxic treatments.
About Children’s Cancer Institute
Originally founded by two fathers of children with cancer in 1976, Children’s Cancer Institute is the only independent medical research institute in Australia wholly dedicated to research into the causes, prevention and cure of childhood cancer. Forty years on, our vision remains unchanged – to save the lives of all children with cancer and to eliminate their suffering. The Institute has grown to now employ more than 220 researchers, operational staff and students, and has established a national and international reputation for scientific excellence.
Our focus is on translational research, and we have an integrated team of laboratory researchers and clinician scientists who work together in partnership to discover new treatments which can be progressed from the lab bench to the beds of children on wards in our hospitals as quickly as possible. These new treatments are specifically targeting childhood cancers, so we can develop safer and more effective drugs and drug combinations that will minimise side-effects and ultimately give children with cancer the best chance of a cure with the highest possible quality of life.
We are currently leading the establishment of the Zero Childhood Cancer national child cancer personalised medicine program for children with the most aggressive cancers, in partnership with the Sydney Children’s Hospitals Network. This program will revolutionise the way treatment decisions are made, with the aim of improving survivorship for those children at highest risk of treatment failure from their disease.