Melanoma Resistance To Combination BRAF And MEK Inhibition Is Driven By Reprogramming Of MAPK Signaling
Funder
National Health and Medical Research Council
Funding Amount
$745,082.00
Summary
Until recently, patients with metastatic melanoma were treated with single agent chemotherapy drugs that produce response rates of less than 10%. New drugs targeting the mitogen activated protein kinase (MAPK) pathway have now shown significant activity, but nearly all patients treated with these new inhibitors eventually develop resistance and progress. This project utilises patient tumour samples to examine the mechanisms of resistance and ways of enhancing the targeted inhibition of the MAPK ....Until recently, patients with metastatic melanoma were treated with single agent chemotherapy drugs that produce response rates of less than 10%. New drugs targeting the mitogen activated protein kinase (MAPK) pathway have now shown significant activity, but nearly all patients treated with these new inhibitors eventually develop resistance and progress. This project utilises patient tumour samples to examine the mechanisms of resistance and ways of enhancing the targeted inhibition of the MAPK signaling cascade.Read moreRead less
New drugs targeting the immune system have dramatically improved the survival of melanoma patients. Nevertheless, 30-40% of patients responding to these new inhibitor will develop drug resistance. This project utilizes patient tumour samples to examine the mechanisms of acquired resistance to immune checkpoint inhibitors. This information will accelerate the identification of novel combination therapies to improve patient outcomes.
Manipulating Oncogene Addiction And Immunity In The Treatment Of Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$687,975.00
Summary
Melanoma is a major Australian health problem and a common cause of cancer death in young adults. Treatment of melanoma has been revolutionised in the last few years, but many patients fail to respond to new therapies or rapidly progress on treatment. This proposal examines the mechanisms that drive resistance to therapy and identifies markers predictive of clinical response. This approach will accelerate the development of new strategies and improve patient care by personalising treatment.
Triple negative breast cancer (TNBC) is an aggressive disease subtype that lacks targeted therapies. We have identified a protein associated with TNBC termed SgK269 that regulates the transmission of signals instructing the cell to grow and migrate. SgK269 associates with a closely-related protein termed SgK223 to form a signalling complex. The aim of this project is to characterise the role of this signalling complex in TNBC and determine whether it represents a potential therapeutic target.
Mechanistic And Functional Characterization Of The Atypical Kinase SgK269
Funder
National Health and Medical Research Council
Funding Amount
$271,879.00
Summary
The overall aim of this study is to characterize at a mechanistic and functional level the oncogenic role of SgK269. We will use quantitative proteomics and phosphoproteomics to characterize the signaling network role of SgK269 and subsequently undertake a detailed structure/function analysis of SgK269 in mammary epithelial cells. Our study will provide novel insights into the signaling mechanism and function of SgK269 and highlight the potential strategies for improved treatment of basal breast ....The overall aim of this study is to characterize at a mechanistic and functional level the oncogenic role of SgK269. We will use quantitative proteomics and phosphoproteomics to characterize the signaling network role of SgK269 and subsequently undertake a detailed structure/function analysis of SgK269 in mammary epithelial cells. Our study will provide novel insights into the signaling mechanism and function of SgK269 and highlight the potential strategies for improved treatment of basal breast cancers.Read moreRead less
Cells have the ability to commit suicide in a process called apoptosis. Developing new treatments and drugs that harness the ability of cancer cells to commit suicide (undergo apoptosis) would represent a new and potentially valuable therapeutic approach. We have identified a number of previously unrecognized ways of triggering apoptosis in cancer cells of the blood (leukemias). We propose to use our approaches to find more effective ways of treating cancers in the future.
While most leukemia patients initially respond well to chemotherapy, >70% die because the disease returns as a result of the survival of leukaemia cells following treatment. We seek to block the switch mechanisms within leukemic cells that allow them to survive current drug therapies. We now seek to examine the therapeutic potential of our discovery with a view toward developing new targetted therapies in the future.
Global Characterization Of The Src-regulated Kinome
Funder
National Health and Medical Research Council
Funding Amount
$591,334.00
Summary
This proposal aims to use new cutting-edge techniques to globally characterize the impact of a particular cancer-causing gene, or oncogene, on the expression and function of an important family of regulatory proteins, termed kinases, in cancer cells. This will identify proteins critical for cancer cell growth and survival that represent potential targets for therapy.
Identification Of Novel Treatment Strategies For Human Cancers Through Integrative Phosphoproteomics And Kinomics.
Funder
National Health and Medical Research Council
Funding Amount
$763,409.00
Summary
This proposal aims to use new cutting-edge techniques to characterize, at a global level, changes in growth regulatory signals in cancer cells. This will identify proteins critical for cancer growth that represent potential targets for therapy. In addition it will highlight ways to select the most effective treatments for individual patients. The ultimate outcome of this work will be improved treatment strategies for cancer patients, and hence reduced morbidity and mortality.