Challenge Grant Award

Challenge grants in scientific research revolve around posing a grand scientific question to the research community and asking researchers to submit their best ideas for meeting the challenge with creative solutions. With help from our Scientific Advisory Board, the Rivkin Center will identify areas in ovarian cancer research in which the greatest strides can be made today and offer a Challenge Grant to the research group that proposes the best solution.

The 2-year, $150,000 Challenge Grant award was conferred for the first time in 2011 due to the generosity of the Smith Family Foundation.

Challenge Grant Award Recipient – 2016

André Lieber, MD, PhD
University of Washington
2016–2017 Lester and Bernice Smith Fellow

Immuno-Prophylaxis of Ovarian Cancer Associated with High-Risk Germ Line Mutations

Dr. Lieber’s project proposes a prophylactic gene therapy approach to introduce genes encoding antibodies into hematopoietic stem cells from the bone marrow. Ovarian cancer cells normally produce signals that inhibit immune cells from attacking and thereby evade destruction by the immune system. Ovarian cancer cells also attract hematopoietic stem cells from the bone marrow which will mature into peripheral blood cells and aid in the growth and metastasis of the cancer cells. The approach of Dr. Lieber’s project is to modify hematopoietic stem cells with genes encoding antibodies against PD-L1 and CTLA4, which are both molecules that inhibit immune system function. If the modified stem cells are ever called upon by ovarian cancer cells, instead of helping the cancer cells to growth, the modified stem cells will produce antibodies that will remove the inhibition of the immune system. The immune system will then be able to function properly and destroy the ovarian cancer cells. This project will demonstrate whether this approach will prevent the development of spontaneous cancer in cancer-prone mouse models of ovarian and breast cancer. Successful results in this study could translate into a future clinical trial available to women at high risk for ovarian and breast cancer. Successful results could also translated to ovarian cancer patients to prevent or delay ovarian and breast cancer reccurrence after standard treatment and may be relevant for treating other types of cancer.

Challenge Grant Award Recipient – 2013

Martin Matzuk, MD, PhD
Baylor College of Medicine

Molecular Imaging of the Dicer/Pten Mouse Model Tumor Microenvironment

Dr. Matzuk’s project will use Dicer-Pten mutant mice, which closely model human high-grade serous carcinoma with tumors arising in the fallopian tubes. A state-of-the-art tissue-based mass spectrometry imaging platform will provide the approach for the in-depth examination of early tumor microenvironment, where tumor cells engage in complex interactions with surrounding non-tumor cells that can both aid and prevent tumor cells from growing and spreading. This project will carefully parse out the spatial distribution of proteins and metabolites during the formation and progression of the earliest ovarian tumors. This knowledge will help identify better treatment alternatives and biomarkers for early detection which will lead to reduced ovarian cancer mortality.

Challenge Grant Award Recipient – 2011

David Bowtell, PhD
Peter MacCallum Cancer Center
2011–2013 Lester and Bernice Smith Fellow

Circulating TP53 mutations as a biomarker of high-grade serous cancer

In his proposed project, Dr. Bowtell will use the latest, most sensitive DNA sequencing techniques to study whether ovarian cancer tumors give off enough DNA into circulating blood to use as an early detection tool. Specifically, the TP53 gene will be examined. Damage to the TP53 gene occurs in essentially 100% of serous ovarian cancers, the most common type of fatal ovarian cancer, and occurs early in the development of the disease. In fact, TP53 mutation is the earliest molecular lesion yet identified in high grade serous cancers, present in intense staining of the fallopian tubes called “p53 signatures” This finding agrees with the most current understanding of serous ovarian cancer which places the origin of this cancer at the fallopian tubes rather than in the ovaries. As a tumor grows, some cells die and release their DNA into circulating blood, including DNA encoding mutated genes. The proposed project by Dr. Bowtell will determine whether circulating TP53 can be detected in circulating blood using advanced genomic techniques. If successful, this novel approach will provide an important diagnostic tool for early detection of serous ovarian cancer – the most common and deadly type of ovarian cancer.