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Colorectal cancer is the third leading cause of cancer related death in Australia. While there are now a number of treatment options for patients with colon cancer, there is significant variability in response among patients to individual drugs. This NHMRC project grant will seek to identify genetic markers which predict the likelihood of a patient responding to a specific therapy. This will enable individual patients to be treated with the drug most likely to be of benefit to them.
Validation Of Formyl Peptide Receptor (FPR)2 As A Target For New Anti-cancer Drugs
Funder
National Health and Medical Research Council
Funding Amount
$588,529.00
Summary
Treatment of breast and other cancers is making incremental improvements, but premature death from this disease and its recurrence in some women after a long period of remission are not adequately treated by current drugs. New work has identified a target called FPR2 that could be used to guide the development of novel drugs. The current project seeks to validate the new drug target, before resource intensive efforts are made to find suitable drugs.
Colorectal cancer (CRC) is one of the most common causes of cancer-associated death in the world. We aim to understand why some CRC patients stop responding to EGFR therapy. In particular, we will study small molecules called cytokines that are produced by the tumour microenvironment and determine if the inhibition of these cytokines can over-come the acquired resistance to therapy. Our goal is to identify new ways to improve the current treatment options for CRC patients.
Stress-induced Genomic Instability As A Driver Of Adaptive Responses In Human Cancer Cells
Funder
National Health and Medical Research Council
Funding Amount
$690,426.00
Summary
Growing experimental evidence suggests human cancer cells use evolutionary conserved programs to regulate their mutation rates in response to pharmacological agents, accelerating adaptation and the emergence of resistance. The purpose of our study is to identify the common molecular pathways and genetic mechanisms driving the regulation of mutation rates. Targeting of these pathways using a new generation of “anti-evolution” drugs is an attractive possibility for novel therapeutic approaches.
Profiling Circulating DNA And RNA To Identify Mechanisms Of Therapeutic Resistance And Response In Metastatic Castration-resistant Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$482,590.00
Summary
Enzalutamide is a powerful hormone treatment that improves survival for men with advanced prostate cancer. Unfortunately, all prostate cancers eventually become resistant to enzalutamide and not all men initially respond to treatment. I will look for blood markers that predict which men benefit from enzalutamide treatment and try to understand how resistance to enzalutamide occurs. This may lead to more effective use of enzalutamide resulting in better outcomes in advanced prostate cancer.
ADAM Metalloprotease Inhibition For Treatment Of Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$770,925.00
Summary
Colorectal cancer (CRC) causes over 4000 deaths/year, typically from developing drug resistance and spreading to other organs (metastasis). These processes involve tumour cells called cancer stem cells (CSCs), which rely on specific cell surface proteins for survival and function. We are developing antibodies against one of these type of proteins, to test in mouse models of CRC. These already show promise in targeting CSCs and inhibiting drug-resistance and metastasis in mice.
Four Dimensional Epigenome Remodelling: Implications For Endocrine Resistance In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$828,560.00
Summary
Patients with estrogen receptor positive breast cancer receive endocrine therapy, however half fail to respond and relapse. Endocrine resistant breast cancer currently represents the most significant challenge to breast cancer treatment. We suggest that three-dimensional epigenetic remodelling is an underlying mechanism that determines endocrine sensitivity that we will exploit as a novel therapeutic strategy to effectively treat patents with recurrent disease.
Tailoring Targeted Therapy To DNA Repair-defective High-Grade Serous Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$802,247.00
Summary
Ovarian cancer is a major cause of cancer death in women because current treatments are inadequate. Half of aggressive ovarian cancers have abnormalities in DNA repair and should be susceptible to new PARP inhibitor therapy, yet not all those respond. By developing a new model of studying human ovarian cancers in mice, we can discover markers to predict which ovarian cancers will respond best to these exciting new treatments.
Targeting Microtubules To Overcome Chemoresistance In Pancreatic Cancer
Funder
National Health and Medical Research Council
Funding Amount
$594,336.00
Summary
Pancreatic cancer is a devastating disease with a dismal prognosis because it is extremely resistant to chemotherapy agents. We plan to examine the expression of proteins called microtubules in pancreatic cancer and assess their role in drug resistance. It is anticipated that the findings of these studies will lead to the development of effective approaches to sensitise the cancer cells to chemotherapy agents.
Real-time Imaging Of Cell Cycle Progression In Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$526,911.00
Summary
Melanoma is the most aggressive skin cancer and is highly therapy resistant, reasons of which are poorly understood. Here we hypothesise that differences in the growth capacity of melanoma cells in different tumour regions contribute to therapy resistance. We will use a novel microscopic system that allows us to visualise division of individual melanoma cells in intact tumours in real time. Using this system, we will test the effects of targeted therapies on melanoma cell growth and survival.