High levels of the HER2 molecule have been identified in 2% of pancreatic cancer cases – indicating new treatment options could be possible via an existing therapy.
Pancreatic cancer is one of the most devastating cancer types, with a five year survival rate of less than 5%. It is also one of the most elusive cancers, with significant variability in molecular behaviour across cases, which dictates how the cancer behaves.
This means that each tumour will only respond to treatments that target its unique molecular blue-print.
But new research, supported with significant funding by the Australian Cancer Research Foundation and published in Genome Medicine, has suggested the treatment ‘Herceptin’ could bring new hope to these pancreatic cancer patients. Herceptin is currently available through the Pharmaceutical Benefits Scheme for breast and gastric cancers with high expressions of HER2, and clinical trials will show whether the drug is equally effective in pancreatic cancer patients.
The HER2 pancreatic cancer sub-group was identified following a series of modern genetics and traditional pathological assessments to estimate the prevalence of HER2- amplified pancreatic cancer.
Teams from the Garvan Institute of Medical Research, the University of Glasgow, and the Queensland Centre for Medical Genomics at the University of Queensland used whole genome DNA sequencing of a HER2 pancreatic cancer sample to identify the specific location of the genome containing HER2.
Then, samples from 462 pancreatic cancer patients were analysed, finding that 2.1% of cases were HER2 positive.
Researchers also found that – like HER2-positive breast cancers – the cancers of those with high levels of HER2 in the pancreas tended to spread to the brain and lung. More typically, pancreatic cancers spread to the liver.
They then extended the study to include sequences from many other types of cancer (available through the International Cancer Genome Consortium and The Cancer Genome Atlas project). HER2 amplification was prevalent at just over 2% frequency in 11 other cancer types.
The implications of this are significant, according to Dr Mark Cowley from the Garvan:
“We make the case that if HER2 is such a strong molecular feature of several cancers, then perhaps recruiting patients to clinical trials on the basis of the molecular features rather than the anatomical region of their cancer could have a significant impact on patient outcomes, and still make economic sense for pharmaceutical companies.”
“Such ‘Basket trials’ as they are sometimes called, may advance treatment options for those with less common cancer types,” he said.
The Garvan Institute in collaboration with the Australasian Gastro-Intestinal Trials Group, is recruiting pancreatic cancer patients for a pilot clinical trial, to test these personalised medicine strategies.
Potential patients will be screened for specific genetic characteristics, including high levels of HER2, and once these characteristics are confirmed, patients will be randomised to receive standard therapy or a personalised therapy based on their unique genetic make-up.
In Australia, 2,000 people are diagnosed with pancreatic cancer each year, and so 40 are likely to have the HER2 amplified form.