A project to improve antibody-drug conjugates for the treatment of HER2-positive breast cancer and another one to distinguish between benign growths and malignant tumors that are precursors to pancreatic cancer have received funding from the Waddell Walker Hancock Cancer Discovery Fund.
Justin Balko, PharmD, PhD, Ingram Professor of Cancer Research and co-leader of the Breast Cancer Research Program at Vanderbilt-Ingram Cancer Center, is leading the breast cancer project. Kathleen DelGiorno, PhD, assistant professor of Cell and Developmental Biology and assistant professor of Surgery, is leading the project to stratify pancreatic cancer risk posed by introductory papillary mucinous neoplasms (IPMN).
These are the second and third grants from the Waddell Walker Hancock Cancer Discovery Fund, which was created in 2022 in honor of the 50th anniversary of the A.B. Hancock Jr. Memorial Laboratory for Cancer Research.
Antibody-drug conjugates are a fast-evolving treatment modality that combine a monoclonal antibody with a cytotoxic drug. The monoclonal antibody binds to a specific protein on cancer cells, allowing the cytotoxic drug to target them and minimize damage to healthy cells. Although antibody-drug conjugates have been approved for HER2-positive and HER2-low breast cancers, the full range of their mechanisms is not understood. The reason for this translational gap is that trastuzumab, the primary monoclonal antibody used in this treatment modality, does not bind to mouse HER2, which is the model system most commonly used in cancer research labs. To address the translational gap, Balko and his research team have developed a new immunocompetent mouse model that has been genetically engineered to permit trastuzumab binding. The work will lay the groundwork for better understanding how antibody-drug conjugates function and improving the therapy.
“We are really excited to have support to continue this project and build off the model we have generated. The new discoveries facilitated by this fund have the potential to lead to new drug combinations in breast cancer and a better understanding of how the drugs work and sometimes cause toxicity, which will help us better optimize therapy in breast cancer patients,” said Balko.
Pancreatic ductal adenocarcinoma, which is the most common type of pancreatic cancer, has one of the highest cancer mortality rates with a five-year survival rate of about 13%. Most patients — 85% — are diagnosed with advanced stage disease when the cancer is incurable. However, about one-fifth of cases arise from IPMN cysts, which are overwhelmingly diagnosed in the premalignant state. Patients with IPMN undergo surgery to reduce their risk of pancreatic cancer, but subsequent pathology reports show that the growths were benign in about half of patients. The surgery to reduce the risk of pancreatic cancer can also be risky with complication rates ranging from 30% to 50% and a 90-day mortality rate of 2%.
DelGiorno, with surgical oncologist Marcus Tan, MBBS, and DelGiorno’s research team, have identified biomarkers that distinguish low-grade from high-grade IPMN. Both markers recognize aberrant glycosylation, which is the process by which sugar molecules attach to proteins and lipids. DelGiorno’s team will develop radiotracers with the Vanderbilt University Institute of Imaging Science and test the hypothesis of whether positron emission tomography (PET) scans can distinguish between high-risk IPMN patient cases who need immediate treatment and surgery and patients who should be monitored and spared a risky surgical procedure.
“We’re honored to be supported by this very generous fund, which will allow us to test whether the markers we’ve discovered can be used to diagnose pancreatic cancer. Development of this PET tracer has the potential to change clinical practice and save lives,” said DelGiorno.
The Waddell Walker Hancock Cancer Discovery Fund supports basic science research projects based on innovative ideas that are considered high-risk with the potential for high rewards. Many donors have given to this endowed fund, which will provide crucial seed funding for Hancock Scholars in perpetuity.
“Our family is proud to continue our longtime support of cancer research at Vanderbilt-Ingram,” said Dell Hancock, daughter of the late Waddell Walker Hancock. “Pancreatic cancer is what drove my mother to start the Hancock Lab over 50 years ago. It’s a full-circle moment to see this fund in her name now supporting Dr. DelGiorno’s research into pancreatic cancer. She would also be inspired by the work of Dr. Balko to treat difficult breast cancers. My mother was always determined to see the lab be a success; she would be thrilled to see the incredible progress made so far.”
To make a gift in support of the Waddell Walker Hancock Cancer Discovery Fund, visit give.vanderbilthealth.org/WaddellWalkerHancock.
