Dr. Philip Spanheimer is an Assistant Professor of Surgical Oncology whose work at UNC began in 2019. He specializes in treatment of breast cancers, complex skin cancers, sarcoma, endocrine surgery, and general oncology. His clinical research focuses on surgical management of cancer and patient outcomes, bringing a patient centered focus to the laboratory to understand disease processes and develop better treatments.
The Spanheimer lab in UNC’s Department of Surgery and Lineberger Comprehensive Cancer Center is interested why some patients with breast cancer respond to treatment and some do not. Understanding how individual cells within tumors adapt to resist therapy will facilitate identification of new treatment strategies to overcome it, which will then understand the interaction and impact of patient factors and surgical management on recurrence, survival, and morbidity of treatment. The focus is to identify patient and tumor characteristics that can help individualize treatment.
The Spanheimer research is funded by a K08 and an R01 grants from the National Cancer Institute, as well as internal funding at the UNC Department of Surgery and the UNC Lineberger Comprehensive Cancer Center. The lab has also received funding from the Society of Surgical Oncology (SSO) and the Society of University Surgeons.
National Academy of Science Publishes Study
There are many ways that ER+ breast tumors become resistant to endocrine therapy, which is the primary treatment. In this study, the researchers are exploring plasticity in intracellular signaling pathways and how these can be targeted in resistant tumors. Ultimately, they hope to understand how tumors become resistant to endocrine therapy and use that to predict patients at risk for treatment failure and develop novel treatment strategies to improve outcomes for patients.
Read more about Dr. Spanheimer’s National Cancer Institute K08 career development award for this study here.
This has been a collaborative effort between Dr. Spanheimer’s lab and the Purvis lab. Focal collaboration with Dr. Jeremy Purvis (Professor, UNC Department of Genetics) and the first authors Sam Wolff (Assistant Professor, UNC Genetics) and Tarek Zikry (PhD student) spotlights research using a multiplex, single-cell imaging platform to identify and characterize differences in cell cycle regulators that allow a subset of ER+/HER2- breast cancer cells to resist CDK4/6 inhibitor mediated cell cycle arrest.
Dr. Spanheimer describes: “Through this analysis we identified a key therapeutic vulnerability of resistant cells – increased dependence on cyclinE/CDK2 activity in cells from a breast cancer cell line and two primary ER+/HER2- breast tumors resected from patients. Co-treatment with CDK4/6 inhibitor and CKD2 inhibitor enhanced cell cycle arrest. Understanding how cells adapt to resist therapy, and targeting dependencies of resistant cells, could lead to improved, more precise, individualized cancer therapies. The funding from the R01 focuses on understanding how plasticity in cell cycle progression underlies resistance to CDK4/6 inhibitors and developing biomarkers of response and therapeutic strategies to overcome resistance”.
The researchers then used this infrastructure to experiment on primary tumors from patients, and the new imaging platform. Through this approach, they identified common changes in cell cycle regulators that facilitated continued cell division and that targeting those pathways enhanced response. This work was a true collaborative effort bringing together researchers with unique backgrounds to study an important problem for patients and make discoveries that can be used to improve how we care for patients. Being able to bring this group together is a primary example of the interdisciplinary collaboration which advances care by surgeon scientists at UNC Surgery and Lineberger.
The team will continue this work with the new R01 grant funds from the National Cancer Institute, focusing on “Cell cycle paths as a framework for understanding drug resistance in tumor cell subpopulations”. Spanheimer is co-investigator with Primary Investigator Dr. Jeremy Purvis. The project goal is to identify remnant of tumor cells after endocrine therapy and CDK4/6 inhibitors; to understand why they do not stop dividing when treated with CDK4/6 inhibitors; and to use this information to predict which tumors will be most successfully targeted by those drugs. This award totals over $3 million dollars between 07/01/2023 – 06/30/2028.
This study recently published in Proceedings of the National Academy of Sciences, is viewable here
Another major study was published in Clinical Cancer Focus in December of 2023. Dr. Spanheimer describes: “We developed a novel model to assess heterogeneity in response of distinct cell populations within primary human breast tumors. Using this model we identified tamoxifen responsive and resistant tumor cell subpopulations within ER+/HER2- breast tumors. By characterizing tamoxifen resistant cell populations we identified unique therapeutic vulnerabilities. Uncovering subpopulations with unique drug sensitivities has the potential to advance precision medicine paradigms by developing precise, patient specific treatment regimens targeting distinct elements within tumors”. (viewable here).
Reflecting upon his grants, focus and collaboration, Dr. Spanheimer emphasizes: “This work demonstrates the power of collaboration and bringing people with different backgrounds together which is a strength of UNC. I’m excited to continue this work in a way that will improve how we treat patients with cancer”.