The research interests of Roxana S. Dronca, M.D., are in the field of tumor immunology, with a particular interest in malignant melanoma and genitourinary malignancies. Her goal is to understand the interaction of immune and endocrine systems in modulating the anti-tumor immune response, study the dynamics and mechanisms of systemic immune regulation in cancer, and develop innovative approaches to cancer therapy utilizing chemotherapy and immunotherapy agents administered in an individualized fashion — synchronized to patient-specific endogenous anti-tumor immune dynamics.
Dr. Dronca's additional research focus is to study the signaling pathway of B7-H1/PD-1 and its role in impaired host immunity in melanoma patients. For this project, Dr. Dronca is closely collaborating with other Mayo Clinic researchers to identify the mechanisms of clinical activity and resistance of these novel immunotherapeutic agents, and to develop and validate immunological biomarkers that could predict response to anti-PD-1/PD-L1 therapies and guide individualized treatment administration.
- Melanoma. This research focuses on understanding the mechanisms of neuroendocrine systemic immune regulation in cancer, and elucidating the bioperiodicity of systemic immunity and the timing of chemotherapy and immunotherapy in metastatic melanoma. Based on this work with other Mayo investigators, the team has found that delivery of cytotoxic-lymphodepleting chemotherapy in unique aspects of this dynamic immunobiologic interaction between systemic immunity and cancer appears to have therapeutic implications in regards to timing of chemotherapy and immunotherapy in patients with metastatic melanoma.
- Tumor immunology. This research focuses on understanding the molecular and cellular regulatory mechanisms in tumor T cell interactions in order to develop effective cancer immunotherapies. Dr. Dronca is particularly interested in the molecular mechanisms by which PD-L1 (B7-H1) promotes tumor survival and impaired function of host immunity in advanced cancers.
- Biomarkers in cancer. Although immune checkpoint PD-1 blockade has recently emerged as an effective therapy for advanced cancer, only a restricted proportion of patients reports durable responses and to date no objective ways to identify targeted PD-1+ T cells responsive to this therapy have been validated. Dr. Dronca has been collaborating to establish the role of Bim expressed by tumor-reactive CD8 T cells and soluble B7-H1 (PD-L1) as new biomarkers to determine the efficacy of anti-PD-1 tumor immunotherapy in patients with metastatic melanoma and other advanced malignancies.
Significance to patient care
Given the variability in response to these novel immunotherapeutic agents and the desire to extend their long-term benefit to more patients, Dr. Dronca has become increasingly aware of the urgent need for the development of biomarkers that can help predict treatment outcomes and ensure that these treatments, which may have significant toxicities, are offered to patients more likely to benefit. Therefore, she has been collaborating on the development of an individualized strategy based on the sensitivity of peripheral blood tumor-reactive PD-1+CD8+ cytotoxic T lymphocytes (CTL) to anti-PD-1/PD-L1 blockade.
The goal is to develop immunological noninvasive biomarkers that would help inform clinical decision-making by selecting patients with melanoma (and possibly other malignancies) who are most likely to benefit from PD-1 and PD-L1 blockade, or early identification of patients who are acquiring resistance during the course of administration.
In addition, one of Dr. Dronca's main goals is to develop innovative approaches to cancer therapy utilizing chemotherapy and immunotherapy agents administered in an individualized fashion, synchronized to patient-specific endogenous anti-tumor immune dynamics, and increase the efficacy of these therapies without added toxicities or costs.
- Associate scientific advisor, Science Translational Medicine, 2015-2016
- Advisory board member, melanoma specialist, Elsevier PracticeUpdate, 2015-present
- Member, Food and Drug Administration (FDA) Cellular, Tissue and Gene Therapies Advisory Committee (CTGTAC), 2015