(L) Dr Robert O’Donoghue, (Centre) Prof Matthias Ernst, (R) Dr Ashleigh Poh

Scientists at the Olivia Newton-John Cancer Research Institute (ONJCRI) have made a ground-breaking discovery that could progress the fight against gastrointestinal cancers, revealing a novel way to suppress the growth of tumours.

Gastrointestinal cancers – those that affect the stomach and bowel – are among the most common causes of cancer death, affecting more than 15,000 Australians each year.

The researchers have shown, in preclinical studies, that inhibiting a protein called HCK (hematopoietic cell kinase) can suppress the growth of established gastrointestinal tumours and reduce the emergence of new cancers.

Prof Matthias Ernst, who led the work with Dr Ashleigh Poh and Dr Robert O’Donoghue, said HCK had a powerful role in cancer development because of the effect it has on macrophages, a critical part of the immune system. “We have known for a long time that in non-cancer situations macrophages have two major roles;” Prof Ernst said. “These cells can behave like ‘garbage collectors’ when they remove unwanted debris or damaged cells, or they can behave like ‘nurses’ to help at sites of injury and wounding.

“What we’ve now discovered is the more HCK activity a macrophage has, the more it nurtures cancer cell growth and survival. The macrophage becomes a wound healer rather than a garbage collector that cleans up the cancer cells.”

Prof Ernst’s team found that inhibiting HCK using a small drug-like molecule reduced the growth of bowel and gastric cancers. Their work is published in the current issue of the international journal Cancer Cell.

Prof Ernst, who is the ONJCRI’s Scientific Director, said drugs that modify the behaviour of macrophages were already starting to show promise as a treatment for solid tumours.

“Our discovery could potentially offer a new and complementary approach to chemotherapy and immunotherapy as options for treating gastrointestinal cancers,” he said.

Dr Niall Tebbutt, Head of Medical Oncology at the Olivia Newton-John Cancer Wellness & Research Centre said the research presented important insight into future treatment approaches for gastrointestinal cancers. “Unfortunately, bowel cancer is generally resistant to conventional immunotherapy treatment,” Dr Tebbutt said. “This research may help us to understand why bowel cancer is so resistant to immunotherapy but, more importantly, it provides a new approach to possibly overcome this resistance through inhibition of HCK. Future clinical trials of this approach in patients with advanced bowel cancer are worth pursuing.”

The Victorian Minister for Health, Jill Hennessy, welcomed the research announcement. “Stomach and bowel cancers are among the biggest killers of Victorians each year and this revolutionary development has the potential to one day save thousands of lives,” Minister Hennessy said. “These ground-breaking results bring us yet another step forward in our fight against cancer, and once again it is researchers here in Victoria leading the way.”

The research was supported by the National Health and Medical Research Council of Australia, Ludwig Cancer Research, La Trobe University and the Victorian State Government Operational Infrastructure Scheme.

Publication details: Poh AR, Love CG, Masson F, et al. Inhibition of Hematopoietic Cell Kinase Activity Suppresses Myeloid Cell-Mediated Colon Cancer Progression. Cancer Cell. 2017;31(4):563-575.e5. doi:10.1016/j.ccell.2017.03.006