Why Is The Bone Marrow A “hot-spot” For Myeloma Plasma Cell Metastasis: Are There Gremlins In The System?
Funder
National Health and Medical Research Council
Funding Amount
$651,979.00
Summary
Most cancer patients die because their cancer spreads from a primary site to other tissues in the body. Once escaping the primary site, 70% of all tumours will spread to bone. This raises the question, why is bone a preferred destination for cancer cells? We provide evidence that Gremlin1, made by non-cancer cells within bone, is a key protein that supports cancer growth. This study will examine whether inhibiting Gremlin1 is a potential therapy to inhibit cancer spreading to bone.
Transcriptional And Epigenetic Regulation Of Epithelial Mesenchymal Plasticity In Breast Cancer Dissemination
Funder
National Health and Medical Research Council
Funding Amount
$670,964.00
Summary
Fuelling the spread of breast cancer are small clusters or individual cancer cells that escape into the blood (CTC) and bone marrow (DTC). Comprehensive analysis of these is prohibited by difficulty in purifying them, and their small numbers. Using two novel, validated mouse models for these cells, we have devised an approach that will identify new diagnostic and therapeutic targets in these compartments. These will ultimately provide avenues to improve breast cancer survival.
Detection Of Metastases In Sentinel Nodes From Patients With Breast Cancer Using Proton Magnetic Resonance Spectroscopy
Funder
National Health and Medical Research Council
Funding Amount
$186,372.00
Summary
The objective is to develop magnetic resonance spectroscopy (MRS) for the rapid and accurate intra-operative detection of cancer cells in sentinel lymph nodes from breast cancer patients. Accurate intra-operative diagnosis of cancer in lymph nodes will enable informed decisions to be made regarding surgery and therapy and reduce the morbidity associated with complete clearance of axillary nodes. Using current histopathological techniques (frozen section) this is not possible. Proton MRS can dete ....The objective is to develop magnetic resonance spectroscopy (MRS) for the rapid and accurate intra-operative detection of cancer cells in sentinel lymph nodes from breast cancer patients. Accurate intra-operative diagnosis of cancer in lymph nodes will enable informed decisions to be made regarding surgery and therapy and reduce the morbidity associated with complete clearance of axillary nodes. Using current histopathological techniques (frozen section) this is not possible. Proton MRS can detect chemicals in malignant cells in lymph nodes with a greater sensitivity than histology and can detect micrometastases in 20 minutes. The MR diagnostic information can be obtained from fine needle biopsies (FNB) making the technique eminently suitable for rapid intra-operative diagnosis. The FNB technique has been shown to be a rapid and accurate method for the assessment of breast lesions, distinguishing benign lesions and invasive cancer with a sensitiviy and specificity of 95% and 96%, respectively. Here we propose to evaluate the use of MRS for the rapid and accurate assessment of sentinel nodes from breast cancer patients. Two blinded studies will be conducted comparing the MRS chemical fingerprints with serial section histopathological data. To evaluate the clinical significance of the MRS diagnosis, all patients will be entered into a prospective study correlating the MRS data with recurrence of disease within 3 and 5 year periods.Read moreRead less
Targeted Alpha Therapy: Development Of A New Treatment For Metastatic Cancer
Funder
National Health and Medical Research Council
Funding Amount
$394,400.00
Summary
Breast cancer is the most commonly diagnosed, malignant cancer in women and prostate cancer is the most common non-life style related cancer in men. In spite of the most aggressive therapy, a significant percentage of men and women die of secondary disease (metastases) which usually spreads in the early stages. Currently, therapy is limited to chemotherapy and hormone therapy, both of which show clinical improvement but long term survival is uncertain. Targeted alpha therapy (TAT) is a new cance ....Breast cancer is the most commonly diagnosed, malignant cancer in women and prostate cancer is the most common non-life style related cancer in men. In spite of the most aggressive therapy, a significant percentage of men and women die of secondary disease (metastases) which usually spreads in the early stages. Currently, therapy is limited to chemotherapy and hormone therapy, both of which show clinical improvement but long term survival is uncertain. Targeted alpha therapy (TAT) is a new cancer treatment that we are developing in mouse models of human breast and prostate cancer. With TAT we are exploiting the fact that aggressive breast and prostate cancer cells, but not normal cells, express a particular tissue-barrier degrading protein system (uPA) which is specifically recognised by a natural inhibitor protein (PAI2). This protein inhibitor is labeled with a highly effective cell killing agent, a radioisotope that emits high energy alpha particles with a short range of only a few cell diameters . The alpha-labeled PAI2 selectively kills cancer cells at their most malignant stage by targeting the uPA system on these cells. Another benefit of TAT is that little radiation damage occurs to nearby or distant normal cells. Thus side-effects would be minimised. The outcome of our research to date has been to show the potential of our unique TAT approach as a possible new therapy for breast and prostate cancer. This therapy may well prove beneficial for other cancers. Further safety evaluations studies in mice will be followed by a dose tolerance clinical trial in humans. We expect to be able to show that our TAT will regress breast and prostate cancer tumours without complications in mice. The human trials will show the tolerance limits to TAT. If successful, TAT could provide the basis for a major change in prognosis and quality of life of breast and prostate cancer patients.Read moreRead less