Molecular mechanisms of rapamycin action on the liver
Liver surgery and transplantation for liver cancer are often associated with damage to the liver, leading to slow recovery and sometimes death. Damage is greater in obese patients. Improvements in surgical and anaesthetic techniques have made liver resection available to patients with a high risk profile, including those with advanced age, obesity and fatty liver disease, and down-staged cancers.
In liver transplantation, donor organ shortage remains a major problem, and the boundaries of marginal donor livers are continuously being explored. Patients with fatty livers as well as older patients are at high risk for ischemia re-perfusion injury (tissue damage upon return of blood supply) in liver resections and liver transplants. Ischemia re-perfusion injury is the major reason for graft dysfunction in liver transplants involving these patients. Limiting the extent of injury would improve the outcome for transplant patients receiving marginal donor livers and for patients with marginal livers undergoing liver resection. Rapamycin, which suppresses the immune system and inhibits cancer growth, is often administered to liver transplant patients. However, its use is controversial since it has both beneficial and detrimental effects. The aim of this research is to better understand the mechanisms of action of rapamycin on the liver and hence provide better outcomes for liver cancer patients and especially to increase the number of usable donor livers.
What we aim to achieve
Presently there are many patients who have liver cancer caused by either development of the cancer within the liver, or as a result of metastatic growth in the liver in the case of advanced colon cancer and cancers in other organs. These liver cancers are often difficult to diagnose in early stages so patients often present with advanced stage cancer. Currently, this can only be treated by liver surgery including liver transplantation. These treatments are associated with increased risk of morbidity and death after surgery and are limited by the availability of donor livers. It is our hope that our research will lead to a situation where most patients can be effectively treated with a good subsequent life expectancy, and where there are no longer liver cancer patients waiting for donor livers because a much wider range of donor livers can be used for liver transplants.
Our next steps and milestones
Cancer Council SA funding has been essential for our research so far. This has allowed us to establish new knowledge of the drugs used to promote better liver function and recovery for liver cancer patients. The next goal of our research is to undertake trials in the surgery and liver transplant unit at FMC to test these new strategies in the clinical situation.
What motivates me
Cancer is an extremely complex disease and is only partially understood. As a result there are many situations where there is either very limited or no treatment options. My motivation is to both assist in gaining a better understanding of the fundamental pathology of cancer and to be able to reduce the number of cases where patients cannot be effectively treated.
My message to supporters
Gaining an understanding of how drugs can be used to improve the treatment of cancer patients is a difficult but essential task if we are to improve outcomes for cancer patients, including those with liver cancer. The processes involved in the development and treatment of cancer are very complex and we are only just beginning to understand these. By contrast many other diseases are simple to understand and treat. Cancer is different. Our lab and others have received great support from Cancer Council SA and we are most grateful for this. To make further progress using state of the art techniques and to develop high quality junior researchers, we need constant and consistent financial help. We believe that in SA we have a better overall research structure for cancer research than previously, involving good collaboration between the Universities Hospitals and SAHMRI. Funds from Cancer Council SA for cancer research are greatly needed to allow research to continue.