Wayne State Researcher Earns $3.1M NIH Grant to Improve HER2+ Breast Cancer Treatment
核心洞察
The National Cancer Institute awarded Wayne State University's Heather Gibson, Ph.D., a five-year, $3.1 million R01 grant to find more effective treatment strategies for HER2+ breast cancer (搜索).
The project focuses on host-intrinsic genetic mechanisms regulating immune activation after targeted immunotherapy, particularly trastuzumab (Herceptin), which binds HER2 (搜索) overexpressed in roughly 20% of breast cancers.
Only about 50% of metastatic HER2 (搜索)+ breast cancers respond to trastuzumab, and the research aims to identify genes that influence immune activation to improve long-term outcomes.
The National Cancer Institute (NCI) of the National Institutes of Health has awarded Wayne State University School of Medicine cancer researcher and principal investigator Heather Gibson, Ph.D. '11, a new five-year, $3.1 million R01 grant to find more effective treatment strategies for patients with HER2+ breast cancer (搜索). Dr. Gibson, an associate professor of Oncology, directs research aimed at identifying genetic factors that influence the immune system and thereby affect treatment response.
The project, titled "Host-intrinsic mechanisms regulating endogenous immune activation after targeted immunotherapy," focuses on anti-tumor antibody therapies such as trastuzumab, which binds to the HER2 (搜索) protein that is overexpressed in approximately 20% of breast cancers. Trastuzumab, commonly known by the brand name Herceptin, is considered the gold standard for treating cancers that express high levels of the HER2 protein, including HER2+ breast cancer (搜索). However, only about 50% of metastatic HER2+ breast cancers respond to trastuzumab, underscoring a significant unmet clinical need.
Dr. Gibson and her team are working to identify new treatment strategies that will help more patients live longer after their diagnosis. "If we can find new ways to activate the patient's T cells to directly eliminate cancer cells, they will have better long-term outcomes," she said. "Our prior work has identified genes that may regulate whether the immune system becomes activated against the tumor after therapy. In the current grant, we will determine how these genes influence immune activity, and we will test whether we can manipulate their function to improve treatment response in animal models, which would set the stage for translating this work to clinical trials. We are also testing clinical samples to determine whether our candidate genes associate with trastuzumab treatment outcomes and/or changes to the immune composition within a tumor."
Genetic Determinants of Treatment Response
Because each patient has unique genetics, the individual immune system may be more or less likely to respond to therapy. Dr. Gibson's research is aimed at identifying genetic factors that influence the immune system and thus affect treatment response, with the team working to understand what differentiates when a patient benefits from treatment.
"If we know the answer to that question, we might be able to introduce new treatment strategies to extend the therapeutic benefit to more patients. We are studying how the genetics of each patient may influence their treatment outcomes, and through this process we have identified potential new candidate targets that might improve the immune response to the cancer," she said.
Translational Potential
Positive results could mean developing new drug combinations that would improve survival rates for patients. "If we are successful, we can design drugs and/or cellular therapies to manipulate these genes and/or their related pathways, which could enhance anti-tumor immunity, particularly when combined with trastuzumab. There is also a chance this strategy might improve other therapies beyond trastuzumab, and we will certainly explore those avenues if warranted by our results," Dr. Gibson said.
Research Foundation and Prior Work
Groundwork for the project began in 2019, using genetically diverse mouse models to identify genes associated with response to anti-tumor antibody treatment. Early on, the team received foundation funding to validate the genes of interest, allowing members to begin looking for mechanisms of action. Two years ago, the researchers received an NIH P20 grant to begin testing for human correlates and determine if genetics play a role in known disparities in HER2+ breast cancer (搜索), work that has further supported the original hypothesis.
"This NIH award recognizes Dr. Gibson's innovative work to address an important clinical challenge in HER2 (搜索)-positive breast cancer," said Wael Sakr, M.D., dean of the Wayne State University School of Medicine. "Trastuzumab has transformed treatment for these patients, yet many do not achieve a lasting response. By uncovering how a patient's genetics and immune system influence treatment outcomes, Dr. Gibson and her colleagues are laying the groundwork for more precise and effective therapies. We are very proud of Dr. Gibson and her team and congratulate them on this outstanding achievement."
Research cited in this article was supported by the National Cancer Institute of the National Institutes of Health under award number R01CA318354.