Surgical Oncology Research

The surgical oncology research section is composed of highly interactive research laboratories focused on developing novel cancer therapies with a bench to bedside translational approach. Areas of priority include:  cancer immunotherapy, tumor angiogenesis, and the development of human tumor models to predict drug efficacy. All three laboratories are highly integrated between themselves and with other research groups within the Hollings Cancer Center.

Surgical Oncology Laboratories

Nancy Klauber-DeMore, M.D. is the BMW Endowed Chair in Cancer Research at the Medical University of South Carolina, Klauber-DeMore has extensive research experience in developing new therapies for breast cancer that have led to clinical advances in patient care, particularly for those with metastatic disease. She has been a principal or co-investigator on more than 30 active and completed clinical trials and has contributed to five patents or patents pending. She is also developing novel surgical devices to aid in breast surgery.

Her lab focuses on discovering novel factors that stimulate the growth of new capillary blood vessels that provide tumors with oxygen and nutrients with a goal of developing new drugs to block these factors, therefore inhibiting tumor growth. She has also played an integral role as a surgeon in the evaluation of surgical clinical trials as well as clinical trials evaluating the role of natural products in cancer treatment.

With a focus on discovering less toxic therapies, Klauber-DeMore is leading investigator-initiated trials that look at the effects of natural products, such as an extract of frankincense, on tumor biology in humans and is collaborating with Mark Hamman, Ph.D., a researcher in Hollings’ Developmental Cancer Therapeutics Program, to generate potent analogues of frankincense.

More recently, research by Klauber-DeMore helped to lead to the development of IVT-8086, a new innovative cancer therapy for the treatment of osteosarcoma. The U.S. Food and Drug Administration granted the drug both the rare pediatric disease designation and orphan drug designation, highlighting the significant unmet medical needs of patients with this life-threatening disease.

Shikhar Mehrotra, Ph.D.

Shikhar Mehrotra, Ph.D., co-scientific director of the CCT, focuses his translational research on understanding T cell biology for improving immunotherapy for cancer. When it comes to treating cancer, cellular therapy is the next frontier. A new clinical trial (ClinicalTrials.gov identifier: NCT05702853) recently opened for recruitment, where patients’ T cells are engineered with CD19 Chimeric Antigen Receptors (CARs) and modified to make them “metabolically fit,” and increase efficacy while reducing toxicity. Similar strategies are being pursued using NCI STTR R41 and R42 funds to generate validation data for new clinical trials that will use tumor-infiltrating lymphocytes (TILs) to treat people with malignant melanoma, breast cancer, and prostate cancer.

In order to generate tumor reactive T cells that can persist longer, and lead to control of tumor growth, the Mehrotra lab is testing several strategies by understanding the overlap that exists between the immune cell signaling pathways and cellular metabolic state associated with it. They previously described a novel strategy to demarcate effector T cells based on cell surface thiol (c-SH) expression into c-SHhi and c-SHlo T cells. They showed high anti-oxidant property is central to potent anti-tumor effector T cells, and directly correlates to CD62Lhi central memory (Tcm), low glycolytic and low mitochondrial membrane potential phenotype, all of which may be linked and contribute to better tumor control. These studies were extended to show the role of thiol regulating molecule thioredoxin in maintaining Tcm phenotype. His group has also shown that p53 regulates T cell glycolysis and altering p53 levels in T cells could be exploited to control tumor growth.

More recently, his group has shown that targeting non-canonical ectonucleotidase CD38 on T cells could lead to a potent and long-term control of tumor mediated by anti-tumor T cells by maintaining higher levels of NAD+ (a cofactor and substrate for various post-translational modifications). His group is also working to combine strategies where targeting kinases with checkpoint blockade could enhance effectiveness of ACT. Another study from his group showed that PIM kinase inhibition leads to drop in glycolysis and maintenance of Tcm phenotype. Further, a combination of PIM kinase inhibitor administered along with anti-PD1 and ACT leads to a robust tumor control. Thus, the overall goal remains to translate the novel pre-clinical approaches targeting immuno-metabolism to clinics for improving the outcomes of T cell based immunotherapy trials.