Improving our understanding of the oncogenic signalling-metabolism nexus to design better treatments for pancreatic cancer
Background
Pancreatic Cancer is one of the most lethal cancers, with only 10% of diagnoses with a five year survivorship, a figure that has not improved significantly in the past 20 years. It is likely that pancreatic cancer incidence and mortality will continue to rise in the next decade, and it is predicted to become the 2nd leading cause of cancer death worldwide by 2030. The poor prognosis associated with the disease stems from several factors, including that it is a highly aggressive cancer which has typically spread to other sites within the body by the time of diagnosis, and that it is proven to be resistant to many established therapies such as chemotherapy. Although surgical removal can be the most effective treatment option for pancreatic cancer, less than 20% of cases involve a tumor that can be surgically resected at the time of diagnosis.
The exceedingly poor survival for pancreatic cancer patients highlights an urgent need to identify new molecular targets and approaches to improve patient outcomes.
About the Project
Professor Turner’s team aims to use cutting edge imaging approaches to shed light on how changes in nutrient metabolism and intracellular signalling contribute to two lethal characteristics of pancreatic cancer, namely chemoresistance and metastatic spread. It is known that both cancer cells and the other supporting cells in the tumour, alter their metabolism to favour a program of uncontrolled growth.
In simple terms, cancer cells need extra nutrient ‘building blocks’ to grow, and they adapt their metabolism to favour the uptake of extra nutrients and the channeling of those nutrients into growth pathways.
There is also emerging evidence that the flexible nature of a cancer cells’ metabolism can also allow for adaptations that help to promote metastatic spread or resistance to specific types of chemotherapies. Knowledge of such changes is very limited in pancreatic cancer and our research will use world-leading analytical and imaging technology to specifically define the metabolic changes that allow cancer cells to be more invasive or reduce their sensitivity to standard of care chemotherapy. An improved understanding of these processes will provide an opportunity to develop new ways to intervene and prevent the spread of pancreatic cancer to distant organs and potentially provide treatment options that will allow chemotherapy agents to work better.
Impact
To begin with, the team expects to be able to identify specific proteins or enzymes that facilitate cancer spread and resistance to chemotherapy. Once identified, the team will be able to study these using modelling to determine their involvement in metastatic spread or development of chemoresistance. This will hopefully allow for the pinpointing of specific vulnerabilities that may be leveraged into therapeutic options to improve the treatment of pancreatic cancer.
Over the long term, the metabolic processes that are shown to be effective targets for mitigating the development of chemoresistance or inhibiting the spread of pancreatic cancer, could become adjuncts for the current standard of care therapies for pancreatic cancer. As metabolic adaptations are recognised as a key characteristic of all cancers, the novel approach employed in this project could be used to identify potential targets of therapeutic relevance in other cancer types.