There is an unmet medical need to develop new therapies that are safer and potentially allow the treatment of a broader range of cancers. Inhibiting the immune checkpoints TIGIT and CD96 represents an opportunity that may parallel and indeed complement the activity and impact of other lymphocyte checkpoint inhibitors in human cancer (eg. PD1/PD-L1). While testing these as targets in mice we will also learn more about their ligand CD155 and their expression in human tumors.
Cellular And Molecular Mechanisms Of Hedgehog Signaling In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$551,937.00
Summary
Breast cancer cells create the conditions for their own survival by communicating their needs to the healthy cells that surround them. We have previously shown that a molecule known as ‘hedgehog’ transmits biochemical signals between breast cancer cells and healthy cells. When hedgehog is ‘silenced’, tumours shrink and stop their spread. In this application, we will identify the cells receiving the hedgehog signal and identify how they support the growth and spread of breast cancers.
Generating Stronger And Smarter T Cells For Cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$310,332.00
Summary
White blood cells from cancer patients can be modified in the laboratory to react against tumours. These cells can then be given back to the patient, which can sometimes cause cancer regression. However, often the white blood cells lack strength, or they lack the ability to distinguish between tumour and normal tissues of the body. In this project we seek to make stronger and smarter white blood cells that can deliver a lethal hit against tumours without damaging essential organs of the body.
Therapeutic Targeting Of MYCN Oncoprotein Stability In Neuroblastoma
Funder
National Health and Medical Research Council
Funding Amount
$590,206.00
Summary
A high level of MYCN protein is a major indicator of aggressive neuroblastoma (NB) but unfortunately there have been many barriers to the design of targeted therapies. We have identified a protein called PA2G4 which is a cofactor for MYCN in promoting cancer cell growth. We have developed a compound which inhibits PA2G4 and MYCN protein levels and reduces tumour growth. We will examine how PA2G4 cause aggressive tumour characteristics and test new methods to block PA2G4.
Identifying Castrate-resistant Tumour Cells In Localised Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$573,047.00
Summary
This proposal addresses one of the most important challenges in cancer: what cell population ‘drives’ tumour progression, and how can it be effectively targeted? We will define the prostate cancer cells that survive androgen withdrawal therapy and investigate new ways to target them. Eliminating these important cells earlier in disease progression will lead to increased survival for men with prostate cancer.
The Ludwig Institute is adopting a two prong approach in the fight against cancer. Ludwig scientists are developing improved and sensitive scanning methods to aid in the conduct of field trials of new anti-cancer antibodies. In addition, they are also developing new targeted anti-cancer antibodies with improved properties that have the ability to bind to tumours while sparing normal tissues. These drugs can either attack the cancer directly or be used to carry drugs to the target thereby shrinki ....The Ludwig Institute is adopting a two prong approach in the fight against cancer. Ludwig scientists are developing improved and sensitive scanning methods to aid in the conduct of field trials of new anti-cancer antibodies. In addition, they are also developing new targeted anti-cancer antibodies with improved properties that have the ability to bind to tumours while sparing normal tissues. These drugs can either attack the cancer directly or be used to carry drugs to the target thereby shrinking the tumour.Read moreRead less
Genetic Engineering Of Tumor-infiltrating Monocytes To Inhibit Primary And Metastatic Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$792,470.00
Summary
The immunosuppressive environment within a tumour is the major impediment to the successful application of cancer immunotherapy. To address this, we developed a cell- and gene-based strategy for targeted delivery of a potent immune-stimulatory molecule, IFN-?, which activates the immune response at the site of the tumour. We now propose to combine this strategy with promising cancer immunotherapies for the treatment of advanced breast cancer and breast cancer metastasis.
Overcoming Resistance To Anti-EGFR Antibody Therapy In Colorectal Cancer Using Novel Targeted PI3K And MEK Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$466,586.00
Summary
Cetuximab treatment is a standard of care for metastatic colorectal cancer, but patients with KRAS, BRAF, PIK3CA or PTEN gene mutated tumours show a lack of response. Newly developed targeted inhibitors against PI3K and MEK may overcome cetuximab resistance. We will perform preclinical studies in cell lines representing the range of mutated tumours found in patients to compare the efficacy of these novel treatments with cetuximab and to characterise the mechanisms underlying drug action.
The Combination Of CDK4 And MAPK/ERK Pathway Inhibitor Therapy In Melanoma: Defining Melanoma Cell Intrinsic And Immune Mediated Responses
Funder
National Health and Medical Research Council
Funding Amount
$824,288.00
Summary
Early-stage melanomas can often be cured with surgery, but more advanced melanomas are harder to treat because standard melanoma treatments do not induce long term disease control. Thus newer types of treatment are required to treat more advanced melanomas. Our proposal will use a drug that stops melanoma cells from growing and in combination with other drugs causes the cells to release factors that activate the immune system to eliminate the tumour.
Exploiting And Defining The Immune Regulatory Activities Of BET Bromodomain Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$923,222.00
Summary
Immune-based agents such as “checkpoint inhibitors” have the ability to re-awaken our own immune systems and activate previously dormant anti-tumor responses. We have discovered that small molecule inhibitors of gene regulatory proteins called bromodomain proteins act synergistically with checkpoint inhibitors in mouse cancer models. We will define the molecular and biological events underpinning this novel combination approach and assess the effects of the combination across different tumors.