Funding Support Center
DF/HCC Sponsored Funding
Dana-Farber/Harvard Cancer Center (DF/HCC) Sponsored Funding
Sponsor: Non-federal (DFCI)
One page Letter of Intent due by February 28, 2013. Submit letter online: Application Form Web Page
Submission requirements: Applications must be submitted online: Application Form Web Page
Please direct questions to:
Career Development Awards will support junior investigators transitioning from training to independent investigators. Research may focus on any aspect of prostate cancer prevention (health promotion, modifiable risk factors, new animal models and extrapolation of these models to human cancer, genetic predisposition to prostate cancer, detection of precursor lesions, chemoprevention, trials in human populations, behavioral research and behavioral intervention trials); epidemiology (classic, genetic, molecular); biostatistics; human cancer genetics; human nutrition; health services and health policy research; and medical decision analysis. Research may also focus on survivorship and quality of life as they relate to prostate cancer; basic and applied research in the behavioral sciences that independently or in combination with biomedical approaches reduces prostate cancer risk, incidence, morbidity, and mortality over the lifespan and across the entire process of carcinogenesis from primary behavioral prevention in youth, to screening, treatment, and survivorship.
Award is for $50,000 per year for up to two years ($100,000 total in direct costs). The next projected award period is August 1, 2013 to July 31, 2015. One award remains in this category to be awarded over a two-year period.
Funding Agency: The funding agency for the program is a grant from the U.S. District Court for the District of Massachusetts. Funding was derived from a pool of unclaimed funds from the settlement in 2004 of a class action suit against TAP Pharmaceuticals. The class action suit was related to marketing and sales practices for the prostate cancer drug Lupron.
The Mazzone Awards Program is a DFCI sponsored award, administered jointly through DF/HCC and the Prostate Cancer Foundation.
ELIGIBILITY AND REQUIREMENTS
Proposals will be accepted from applicants in their final year of clinical fellowship or postdoctoral fellowship (MD, PhD, or MD/PhD) or within their first three years on staff, or in an academic appointment not higher than Assistant Professor at Harvard. A track record of interest and productivity in prostate cancer research is required. Awardees will be encouraged to apply for DF/HCC membership and will be invited to attend program activities (meetings, retreats, research presentations). Applications including investigators from more than one DF/HCC member institution will be encouraged. Applicants are also encouraged to have collaborators at other institutions throughout the country.
Past or present recipients of a Prostate Cancer Foundation young investigator award or DF/HCC Specialized Programs of Research Excellence (SPORE) career development award are not eligible for this Mazzone award. Employees or subcontractors of a government entity or for-profit private industry are not eligible. Exceptions include applicants holding full-time positions at a veterans' hospital or national laboratory (e.g., Lawrence Berkeley National Laboratory) in the United States. Members of the Program’s Scientific Advisory Board (SAB) are ineligible to apply.
PROPOSAL SUBMISSION INFORMATION
Format: Items 2 – 7 (above) must be compiled and submitted as a single PDF file. Please include the PI’s name, project title, and page number at the top of each page. The 3 page research proposal should include an introduction, specific aims, and research strategy (significance, innovation, and approach). Use standard size paper (8 ½” x 11”), Arial or Helvetica font, 11 points or larger with margins ½ inch or larger (top, bottom, left, and right). Figures and legends must be of legible size and legible when printed in black and white.
Submit Proposal Online: Application Form Web Page
2012 Career Development Mazzone Awards Recipients
Approximately 36-70% of prostate cancer patients harbor disseminated tumor cells in bone marrow prior to radical prostatectomy, though only a fraction will develop overt bone metastases. Our understanding of the biological mechanisms underlying the progression of metastatic disease has been limited in part by the difficulty in obtaining bone lesions for research purposes and the molecular heterogeneity of primary and metastatic tumors. The few studies that have explored gene expression patterns in bone metastases versus primary tumor identified multiple general pathways that could be implicated in metastatic progression. We plan to identify a more focused and biologically relevant gene signature of metastatic progression by integrating online data mining tools of existing studies with gene expression data from our study population of 15 patients with matched specimens of bone marrow metastases and primary tumors. First, we will use the ncbi gene expression omnibus (geo) to construct our candidate gene list of ~800 transcripts to test in our study population. We will then put our findings in a biological context in 3 ways: 1) using bioinformatics techniques to detect which genes or pathways we identify are present in current prognostic signatures; 2) using a separate patient population to test whether our signature distinguishes lymph node metastases from primary prostate tumors; and 3) using the broad institute’s connectivity map to screen for drugs that could potentially alter our gene targets. Overall, our study provides a focused, innovative approach toward identifying therapeutic targets to prevent and treat metastatic prostate cancer.
2011 Career Development Mazzone Awards Recipients
Probing androgen receptor signaling in circulating tumor cells in prostate cancer
Prostate cancer progression critically depends on a molecular signaling pathway called the androgen receptor (AR) pathway. The first-line treatment for metastatic prostate cancer is hormonal therapy, which works by turning off the AR pathway in cancer cells and preventing their growth. Several promising new prostate cancer drugs also target the AR pathway, but with even greater effectiveness. However, at the present time, there are no reliable assays to determine whether or not these drugs are working effectively during treatment. This project proposes to use a new technology called the “CTC-chip,” which isolates cancer cells circulating in the bloodstream of patients (circulating tumor cells, or CTCs), to perform molecular tests to determine whether cancer drugs are properly hitting their target. Specifically, the project will use the CTC-chip to isolate CTCs from patients with advanced prostate cancer before and after hormonal therapy, and perform tests on these CTCs to determine whether the AR pathway has been effectively turned off. In addition, the project will examine AR signaling activity at the single cell level using a combination of high resolution imaging and sophisticated molecular analyses. If successful, these studies may provide a blood test that can show whether hormonal therapy is effectively attacking a patient’s prostate cancer, and will yield new scientific insights into the AR signaling pathway that may provide clues to new approaches to prostate cancer treatment.
Prostate cancer is known to be highly heritable; numerous germline genetic variants have been identified through genome-wide association studies that are significantly associated with PCa risk. However, the function of these genetic variants and their biological mechanisms are generally unknown. mRNA expression levels can offer clues to these mechanisms, providing insight into opportunities for prevention. Additionally, men with specific genetic risk variants may be more likely to develop particular molecular subtypes of Prostate Cancer. This prospective study of 413 men with Prostate Cancer will assess the association of each confirmed Prostate Cancer germline risk variant with the mRNA expression of 29,000 gene targets in prostate tumor and adjacent normal tissue to identify possible genes and pathways involved. The study will also examine the association of the risk variants with the most common and relevant Prostate Cancer molecular alterations, TMPRSS2:ERG fusion, loss of PTEN, and MYC amplification. This comprehensive study will ascertain biological pathways that explain the link between genetic risk variants and Prostate Cancer; identifying these genes and pathways is a necessary step in developing targeted therapies. If a man’s genetic risk variant profile makes him more susceptible to developing specific molecular subtypes of Prostate Cancer, this new information could influence treatment choices among men carrying these particular risk variants.
Phosphorus and calcium intake, tumor microenvironment and prostate cancer progression
Prostate cancer mortality is often due to bone metastasis, which occurs frequently in Prostate Cancer. Factors that increase the affinity of tumor cells for bone are likely to be related to prostate cancer progression and mortality. Previous findings have suggested that bone-related nutrients (calcium, vitamin D, phosphorus) may be risk factors for prostate cancer. The Health Professionals Follow-up Study found that higher dietary intakes of calcium and phosphorus are associated with increased risk of prostate cancer, particularly with more aggressive forms of the disease. This project hypothesizes that calcium and phosphorus intakes may influence tumor cell expression of bone metabolism-related proteins: osteopontin, calcium-sensing receptor, PTH-related protein, and its receptor, all of which have been linked to bone metastasis and cancer progression. This project proposes to study this hypothesis using the Health Professionals Follow-up Study, which has a unique combination of data on dietary habits of men before and after prostate cancer diagnosis, prostate cancer tissue specimens, and long-term follow up of patients. This will allow a study of the relationship between dietary phosphorus and calcium intakes and tumor expression of bone-related proteins, and how these factors relate to long-term survival in prostate cancer patients. By combining diet, tumor tissue, and survival information, this unique patho-epidemiology investigation will help to clarify previous results on the role of diet in prostate cancer, support public health efforts to improve prostate cancer survival, and shed light on underlying disease mechanisms.