Hollings Clinical Scholars

Current Scholars

Implementation of a Pilot Program for Opportunistic Salpingectomy at the Time of Gastrointestinal Surgery at MUSC: An Evaluation of Patient and Provider Knowledge and Attitudes

The goal of this research is to assess the knowledge and attitudes of patients and GI surgeons regarding opportunistic salpingectomy (removal of fallopian tubes to prevent ovarian cancer) and to implement an opportunistic salpingectomy pilot program to assess feasibility and outcomes at MUSC. 

Development and Implementation of a Novel Shared Decision-Making Tool to Support Cancer Care Delivery Concordant with Patient Treatment Preferences

Most shared-decision making (SDM) interventions are designed to improve provider delivery of knowledge to the patient. I aim to improve the balance of information in SDM models by empowering patients to share their care goals with providers. I will (1) study the process of implementation of a previously developed SDM tool and (2) develop a patient-centered SDM tool to facilitate patients sharing what their care goals are, as they undergo treatment for lung cancer. 

An Equity Focused Intervention to Improve Utilization in Guideline Concordant Extended Venous Thromboembolism Prophylaxis After Major Cancer Surgery

While blood clots after major cancer surgery are common and harmful to patients, the medications available to decrease blood clot risk are seldom used. Blood clots may play a role in observed racial disparities for cancer patients though little is known about this. We will perform an educational intervention to improve surgeon use of these medications to reduce the risk of blood clots after major cancer surgery and potentially reduce disparities in cancer outcomes.

Previous Scholars

Improving the Timeliness and Equity of Adjuvant Therapy Following Surgery for Head and Neck Cancer

My research aims to decrease mortality and reduce disparities in outcomes among racial/ethnic minorities and other medically underserved populations by improving the timeliness, equity, and quality of cancer care. In this project, we are conducting a clinical trial to assess whether a new way of structuring cancer care delivery to patients with head and neck cancer can improve the receipt of timely combinations of surgery, radiation, and chemotherapy and decrease racial disparities in treatment delays.

Development of a Comprehensive Program of Clinical Investigation in CTCL and its Underlying Genetics

Cutaneous T-cell lymphomas (CTCL, including Mycosis Fungoides and Sezary Syndrome) are rare types of lymphoma that are unique in their predominate involvement of the skin. They can range from very slow-growing and easily managed to very aggressive variants that are debilitating and life limiting. In contrast to the more common B-cell lymphomas, CTCL is poorly understood with the biology and underlying genetics poorly defined — resulting in therapies that are not as efficacious nor targeted as its B-cell counterparts. We seek to develop a framework on which we can build a program of clinical investigation into the underlying biology of CTCL and treatment effects.

Improvement of Check-Point Inhibitor Efficacy in Metastatic Osteosarcoma with Anti-SFRP2 Therapy

In 2008, the Klauber-DeMore laboratory made the discovery of the overexpression of a protein called secreted frizzled related protein 2 in human breast cancer. They subsequently developed a humanized monoclonal antibody to SFRP2 that blocks tumor growth in pre-clinical models. Further work has discovered a profound effect of this antibody in tumor immunology. A recent study found that SFRP2 is very important in osteosarcoma metastases. The purpose of this project is to combine the SFRP2 monoclonal antibody with standard immunotherapy for the treatment of osteosarcoma.

Novel Approaches for the Treatment of Metastatic Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) represents 15-20% of all breast cancers and is characterized by elevated genomic instability that can require an aggressive clinical course compared with other subtypes. Immunotherapy is emerging as a new treatment in breast cancer. Boosted by the exciting recent advances in the field of immuno-oncology and breast cancer, Giordano and colleagues proposed a translational program concentrating in these areas that would have a significant potential to lead to cancer discoveries. In this project, they will investigate two novel combinations for the treatment of stage 4 TNBC patients:

• The addition of a colony-stimulating factor-1 receptor (CSF-1R) inhibitor (SNDX-6352) to immunotherapy drug durvalumab to enhance the effect of checkpoint inhibitors in breast cancer.
• A novel combination of an orally available PLK1 inhibitor (onvansertib) and paclitaxel — based on the preclinical data obtained during the Hollings K12 program, aimed at career development in clinical and translational oncology.

Oral Azacitadine (CC-486) plus Salvage Chemotherapy in Relapsed/Refractory Diffuse Large B-cell Lymphoma

Diffuse large B-cell Lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL), with over 27,000 patients diagnosed in 2016 in the U.S. Unfortunately, 35-40% of patients are not cured with initial chemotherapy. Intensive (salvage) chemotherapy followed by autologous stem cell transplant (ASCT) is the standard treatment for relapsed DLBCL. Only 50-65% of patients will achieve an optimal response following salvage chemotherapy to proceed to ASCT. More effective salvage regimens to overcome chemotherapy resistance are needed. This project will investigate the addition of a novel drug (CC-486 ) to chemotherapy prior to ASCT in efforts to enhance chemotherapy sensitivity and increase the likelihood of cure.

Characterization of the Role of the Angiogenic Factor SFRP2 in Thyroid Cancer

There are several types of thyroid cancer, and those of the same type may be more or less aggressive in nature. The reason for this variability is unknown. This project focuses on investigating a molecular factor, SFRP2, that may be involved in the development of aggressive thyroid cancer. This angiogenic factor has been shown to be involved in several malignancies, including breast cancer and melanoma, is expressed in thyroid cancer, and its effect on thyroid cancer growth will be characterized.

Acute leukemia remains one of the leading causes of death from blood cancers. Advances in the field, including stem cell transplant and new targeted drug therapies, have improved the outcomes for many patients with acute leukemia. However, access to such innovative therapy and complications of therapy continue to be barriers to the goal of finding the cure. Randolph's interests include the application of both cellular and pharmacologic therapy for blood cancers. His research is focused on acute leukemia, health disparities, and complications of stem cell transplant. His current research project involves the development of a database of patients with blood cancers to help identify disparities in the care of such patients and opportunities for clinical trials for patients with leukemia. He is also engaged in research related to the prevention and treatment of graft-versus-host disease.

Integrating Basic and Clinical Research in Oral and Oropharyngeal Squamous Cell Carcinoma (OPSCC): A Prospective Non-Randomized Study by the Head and Neck Oncology Group at MUSC

This project will integrate clinical, basic, and translational research studies and focus on mouth and throat cancers, including HPV-related cancers. The team will investigate the link of cancer molecules with clinical outcomes in head and neck cancer patients.

Targeted Therapy for Aggressive Variant Prostate Cancer

Dr. Lilly will investigate antibody-targeted chemotherapy for a newly recognized form of prostate cancer, called aggressive variant or neuroendocrine prostate cancer. This project will utilize a new biomarker (blood test) to identify patients for a corresponding clinical trial and investigate new combinations of the antibody-targeted chemotherapy drug with other anticancer agents.

Impact of Radiotherapy on Immune Modulation by Dual Checkpoint Inhibition in Bladder Cancer

Dr. Marshall and members of the Genitourinary team will be studying ways in which radiation therapy can maximize the body’s own immune response to fight bladder cancer when combined with two new checkpoint inhibitor immunotherapies.

Defining the Role of Major Histocompatibility Class I Expression in Tumors as a Determinant of CD8+ T Cell and Natural Killer Cell Response in Patients Receiving a Novel Therapeutic Combination of Anti-PD1 mAb and an IL-2 Common Gamma Chain Agonist

Immunotherapies are treatments for cancer intended to encourage the patient’s own immune system to fight cancer and represent the area of greatest growth in cancer research today. This project intends to understand which lung cancer patients benefit from the addition of cytokine therapy to FDA-approved PD-1 mAb therapy and how this novel combination may help circumvent a tumor’s mechanisms of escape from the immune system.

Modeling the Human Tumor-Immune Axis Using a Novel Rectal Cancer Patient-derived Xenograft Platform

This project will address the limitations of current tumor immunology animal models in an effort to fast-forward colorectal cancer translational research. Our multidisciplinary team developed a novel mouse tumor model using the patient’s tumor cells and their own immune cells to recreate the tumor immune system. We will use these patient-derived cancer models to explore factors regulating the tumor immunity and to design future immunotherapy strategies.

Development of Novel Genomic Signature of Genes Driving Oncogenic Mutations in p53

Over 70% of squamous cell carcinoma of the head and neck have mutations in the tumor suppressor gene TP53. Previous research has identified a subset of these mutations are associated with aggressive disease and decreased patient survival, but it is not currently understood how these mutations make head and neck tumor cells more invasive. The research proposed in this application aims to develop a genomic fingerprint of genes driving the cancer causing p53 mutations that can be applied to tumors of patients with head and neck cancer through the novel integration of functional and descriptive genomic data.

Phase II Randomized Trial to Evaluate the Safety and Efficacy of Pertuzumab and Trastuzumab plus Ribociclib and an Aromatase Inhibitor or Fulvestrant as Therapy for HER2-positive and HR-positive Metastatic Breast Cancer (PETRA)

Dr. Giordano will design a clinical trial asking a very important clinical question; to determine if chemotherapy is needed for the first-line treatment of metastatic HER2-positive/ hormone (HR)-positive breast cancer. Dr. Giordano’s trial will determine if targeted therapy with HER2-directed therapy plus endocrine therapy is as effective and also improves a woman's quality of life compared to the current standard of care, including chemotherapy plus HER2-directed therapy. Dr. Giordano's trial has the potential to change clinical practice.

L-serine Therapy in the Prevention of Taxane-induced Peripheral Neuropathy

L-serine is important in preventing high levels of abnormal lipids thought to contribute to nerve damage. In an effort to prevent and reduce nerve damage caused by chemotherapy, this study will test the effects of amino acid L-serine given to breast cancer patients receiving chemotherapy as well as examine whether similar lipid level changes occur in prostate cancer patients receiving chemotherapy.

Umbrella Trial for Recurrent Endometrial Cancer

Endometrial cancer is the most common gynecologic malignancy in the United States, and while women who present with localized recurrence fare well with surgery and/or radiation therapy, women who relapse following first- or second-line chemotherapy have a poor prognosis with limited treatment options. As part of the Clinical Scholar Program, I am developing a phase II clinical trial protocol for a DNA Damage Response Agent plus an Immuno-oncology agent as part of an umbrella trial for recurrent endometrial cancer. I will also be evaluating potential biomarkers of response to this combination therapy.

Reviewers

Internal

• Andrea Abbott, M.D., MSCR
• Steven Carroll, M.D., Ph.D.
• Nancy Klauber-DeMore, M.D.
• Michelle Hudspeth, M.D.
• Lee Leddy, M.D., MSCR
• Shikhar Mehrotra, Ph.D.
• James Ravenel, M.D.
• Gerard Silvestri, M.D.
• Kenneth Tew, Ph.D.
• Graham Warren, M.D., Ph.D.

External

• Gregory Kennedy, M.D., Ph.D. 
  • University of Alabama School of Medicine
• Edward Newman, Ph.D. 
  • City of Hope
• Lillian Siu, M.D.
  • Princess Margaret Cancer Center, University Health Network