Hematology Oncology Grand Rounds

The MUSC Hollings Cancer Center Hematology Oncology division hosts weekly Grand Rounds presentations on a variety of topics relevant to the field. Speakers include MUSC faculty as well as faculty from other institutions around the country. Select presentations are curated below.

March 2025 Grand Rounds

March 14

"The MYC Oncoprotein in Aggressive Liver Metastatic Pancreatic Cancer"

Dr. Rosalie Sears discussed the role of the MYC oncoprotein in driving aggressive, liver-metastatic pancreatic cancer. She explained that MYC, often hyperactivated in pancreatic cancer through mutant KRAS signaling, functions as a master gene expression regulator. Using a genetically engineered mouse model, her team showed that co-expression of MYC and oncogenic KRAS leads to rapid tumor growth and liver metastasis. Dr. Sears highlighted the significance of MYC phosphorylation at serine 62 (S62), a modification that stabilizes MYC and enhances its oncogenic activity. Tumors with high phospho-MYC S62 levels exhibited increased replication stress, DNA damage, and immune suppression. Importantly, S62 phosphorylation allows MYC to localize to DNA double-strand breaks and support DNA repair, helping cancer cells survive despite genomic instability. Her findings underscore the central role of MYC in both intrinsic tumor progression and modulation of the tumor microenvironment, offering insight into potential therapeutic targets for aggressive pancreatic cancer.

Rosalie C. Sears, Ph.D.
Professor, Molecular and Medical Genetics
Krista L. Lake Chair in Cancer Research
Co-Director, Brenden-Colson Center for Pancreatic Care
Knight Cancer Institute

March 7

"Best Practices in Feedback and Evaluation Across the Education Continuum"

Dr. Marc Heincelman, along with other contributors, led a discussion on best practices for giving and receiving feedback in medical education. Emphasizing that effective feedback is essential for learner growth, the session focused on making feedback timely, behavior-specific, interactive, and free from high-inference judgments. Dr. Heincelman advocated for the use of structured frameworks like "CLEAR" (Clinician, Leader, Efficiency, Academic Educator, Relationships) and encouraged educators to engage learners in self-assessment and action planning. He addressed common challenges such as unconscious bias, particularly regarding gender and underrepresented groups, and the importance of recognizing external factors that may affect struggling learners. The talk also explored strategies for upward feedback to supervisors, recommending clarity in expectations and open dialogue. Overall, the session highlighted feedback as a two-way, ongoing process aimed at continuous improvement and professional development.

Marc Heincelman, M.D., MPH
Assistant Professor of Medicine
Assistant Dean for Career Advising, College of Medicine
Director, Division of Hospital Medicine
Medical University of South Carolina

February 2025 Grand Rounds

February 14

"Leveraging Genomics to Improve Breast Cancer Outcomes in Diverse Populations"

Dr. Sonya Reid discussed the role of genomics in improving breast cancer outcomes among diverse populations, with a focus on addressing racial disparities. She highlighted that Black women face a 40% higher breast cancer mortality rate than white women, despite a lower incidence of the disease, and that these disparities persist even after accounting for socioeconomic factors—pointing to underlying biological differences. Dr. Reid explained that Black patients are more likely to develop aggressive subtypes, such as basal-like and luminal B tumors, even within hormone receptor-positive, HER2-negative breast cancer. She discussed the utility of genomic assays like Oncotype DX and PAM50 in identifying high-risk patients who may benefit from chemotherapy, but noted that outcomes still differ by race, even when genomic risk scores are similar. To address these issues, Dr. Reid is leading the INSIGHT trial, which uses genomic testing to guide treatment decisions in metastatic hormone receptor-positive breast cancer, with an emphasis on enrolling a diverse patient population. She underscored that without greater representation in clinical trials, it will be impossible to fully understand and address the biological and non-biological drivers of racial disparities in breast cancer outcomes.

Sonya Reid, M.D., MPH
Assistant Professor of Medicine, Breast Oncology
Vanderbilt-Ingram Cancer Center

February 7

"Gene Therapy for Sickle Cell Disease"

Dr. Jean-Antoine Ribeil presented an overview of gene therapy approaches for treating sickle cell disease and beta-thalassemia, focusing on both gene addition and gene editing strategies. He explained that these inherited blood disorders can be addressed by either inserting a functional beta-globin gene or editing the BCL11A gene to boost fetal hemoglobin production. Early clinical trials using lentiviral gene addition showed encouraging outcomes, including sustained anti-sickling hemoglobin production and fewer vaso-occlusive crises, though challenges like repeated bone marrow harvests and low vector copy numbers initially limited success. Advances in manufacturing have since improved these results. Dr. Ribeil also discussed gene editing using CRISPR/Cas9, which has demonstrated strong potential by producing high levels of fetal hemoglobin and reducing disease symptoms. While both approaches show promise as transformative therapies, he noted the importance of monitoring long-term safety, particularly in light of rare but serious adverse events such as myelodysplastic syndrome and leukemia. Overall, he emphasized that while not yet curative, gene therapies represent a major step forward in the treatment of these hemoglobinopathies.

Jean-Antoine Ribeil, M.D., Ph.D.
Former Director of Sickle Cell Center at Boston Medical Center
CEO GLOB Therapy Consulting

January 2025 Grand Rounds

January 10

"Functional interrogation of an essential high-plasticity cell state in lung cancer reveals a dependency on NF-kB"

Dr. Jason E. Chan discussed his research on tumor cell plasticity in lung adenocarcinoma and its implications for cancer maintenance and treatment. His work identified a “high plasticity cell state” that arises early in tumor development, makes up a small fraction of tumor cells, yet plays a critical role in sustaining tumor growth by generating other cell states. Using mouse models and patient-derived samples, Dr. Chan demonstrated that this plasticity is driven by the canonical NF-κB signaling pathway, specifically the p50/p65 complex. Targeting this cell population through genetic ablation or immunotherapy, particularly in combination with standard treatments like chemotherapy or KRAS inhibitors, significantly reduced tumor burden and improved therapeutic outcomes. His findings highlight the importance of targeting tumor plasticity as a strategy to enhance lung cancer treatment and better understand tumor heterogeneity and resistance.

Jason E. Chan, M.D., Ph.D.
Clinical Instructor, Sarcoma Medical Oncology Service
Memorial Sloan Kettering Cancer Center

December 2024 Grand Rounds

December 20

"Mechanistic Antigens in Fusion Protein-Initiated NUT Carcinoma: Finding the Ben Brown Antigen"

Dr. Jensen discusses a rare and aggressive cancer caused by the NUT-BRD4 fusion protein. He explores potential immunotherapy approaches, particularly T-cell receptor bispecific (TCR therapies), hypothesizing that nut carcinoma expresses cancer-testis antigens, making it a target for immune-based treatments. His research involves T-cell killing assays, RNA sequencing, computational antigen predictions, and immunopeptidomes (mass spectrometry) to identify actual tumor antigens. The ultimate goal is to develop targeted therapies for nut carcinoma using HLA-restricted treatments.

Jeff Jensen, M.D., Ph.D.
Physician Scientist Training Program
Division of Medical Oncology, Department of Medicine
University of North Carolina

December 13

"First Line Systemic Therapy in Metastatic Clear Cell Renal Cell Carcinoma"

Dr. Selvakumar discusses first-line systemic therapy for metastatic clear cell renal cell carcinoma (ccRCC), emphasizing key clinical trials. ccRCC is the most common kidney cancer subtype, with pathogenesis largely driven by VHL gene mutations on chromosome 3p. Three key pathways—VHL-HIF, mTOR-PI3K, and PD-1/PD-L1—drive tumor growth and serve as therapeutic targets.

Tharakeswari Selvakumar, M.D., Ph.D.
Hematology Oncology Fellow PGY5
Medical University of South Carolina

November 2024 Grand Rounds

November 22

"Personalized Strategies will Improve Survival for Pancreatic Cancer"

Dr. Hawkins discusses the importance of team-based research in advancing pancreatic cancer treatment, with a focus on immunotherapy’s potential to improve patient outcomes. He emphasizes the challenges of pancreatic cancer, including its low survival rates, resistance to chemotherapy, and immunosuppressive tumor microenvironment.

William G. Hawkins, M.D.
Deputy Director, Hollings Cancer Center
Vice Chair for Clinical Affairs, Department of Surgery
AR Folk Professor of Surgery

October 2024 Grand Rounds

October 18

"Atypical Hemolytic Uremic Syndrome (aHUS): An Overview on Diagnosis, Treatment and Management"

Dr. Melèndez discusses atypical hemolytic uremic syndrome (aHUS) a rare, chronic disease characterized by complement system dysregulation leading to endothelial damage, prothrombotic state, and organ dysfunction, primarily affecting the kidneys. Unlike typical HUS, which is more common in children and triggered by infections like Shiga toxin-producing E. coli, aHUS accounts for about 10% of cases and often has a genetic basis. Mutations in complement regulatory proteins, such as factor H, factor I, and complement C3, contribute to disease pathogenesis, though not all carriers develop the disease without additional triggers like infections, medications, or pregnancy.

Yiseiry Pèrez Melèndez, M.D.
Hematology and Oncology Fellowship
Hollings Cancer Center
Medical University of South Carolina

October 4

"Evidence-based Medicine: Possible lessons for oncology"

Dr. Guyatt discusses the importance of evidence-based medicine (EBM) and how historical reliance on expert recommendations, rather than systematic evidence, has led to significant medical errors. He illustrates this with examples from cardiovascular medicine, including thrombolytic therapy for myocardial infarction and prophylactic lidocaine use.

Gordon Guyatt, M.D.
Clarity Research Group
Department of Clinical Epidemiology
McMaster University

September 2024 Grand Rounds

September 20

"Management of FLT3-Mutated AML in 2024"

Dr. Medawar discusses the management of FLT3 mutated Acute Myeloid Leukemia (AML) in 2024, focuses on advancements and treatment options for patients with this condition. He provides an overview of clinical cases and treatment approaches, highlighting various challenges and decisions in treating AML patients.

Georgio Medawar, M.D.
Hematology-Oncology Fellow
MUSC Hollings Cancer Center

August 2024 Grand Rounds

August 23

"The Spectrum of Anti-PF4 Disorders in 2024"

Dr. Warkentin discusses the awareness of the diagnosis and treatment of classic HIT (cHIT), autoimmune HIT (aHIT), spontaneous HIT (SpHIT), VITT, and VITT-like disorders (acute, chronic). He discusses various anti-PF4 disorders, focusing on the differences between classic heparin-induced thrombocytopenia (HIT) and vaccine-induced thrombocytopenia (VITT). Both conditions involve the PF4 protein, which, when bound to heparin, forms immune complexes that trigger platelet activation. Classic HIT is associated with antibodies targeting the "North and South Poles" of the PF4 molecule, while VITT involves antibodies targeting the "equator" or heparin binding site of PF4. The distinction between these antigen targets is critical to understanding the differing mechanisms of the two disorders. Dr. Warkentin also suggests that HIT may have evolved as an antibacterial immune response, with heparin complexes activating the immune system through various mechanisms involving B lymphocytes and monocytes.

Theodore (Ted) Warkentin, M.D.
Professor Emeritus
McMaster University
Hamilton, Ontario, Canada

August 16

"Identifying a gene signature of metastatic potential by linking pre-metastatic state to ultimate metastatic fate"

Dr. Handler discusses metastasis, specifically in pancreatic cancer (PDAC), and the challenges in studying it. Outlines the steps involved in the metastatic cascade, from primary tumor cell invasion to successful colonization of secondary sites. He introduces an experimental method developed to capture pancreatic cancer subclones and characterize their metastatic potential, leading to the discovery of a gene signature for metastasis.

Jesse Handler, M.D., Ph.D.
Medical Oncology Fellow
Johns Hopkins University

August 2

"Evaluating Novel Cancer Therapeutic Strategies Using Living Tumor Biopsies"

Dr. Jenkins discusses a novel approach using patient-derived tumor spheroids (PDOTS) grown in a microfluidic system allows real-time observation of tumor responses to drugs and immune cells, mimicking human tumor physiology. This system has been enhanced with quantitative techniques like immunophenotyping, single-cell RNA sequencing, and cytokine profiling, offering improved insights into tumor growth and immune interactions, and holds promise for advancing personalized cancer treatments.

Russell W. Jenkins, M.D., Ph.D.
Mass General Cancer Center | Harvard Medical School
Center for Melanoma, Termeer Center for Targeted Therapies
Krantz Family Center for Cancer Research, Center for Cancer Immunology

June 2024 Grand Rounds

June 7

"Unmet needs in Peripheral T-cell Lymphoma"

Dr. Gurumurthi discusses the challenges in diagnosing and treating peripheral T-cell lymphoma (PTCL), which comprises 10-15% of lymphoma cases and lacks reliable markers of clonality. It = highlight the importance of a collaborative approach between pathologists and clinicians, using a case of ALK-negative anaplastic large cell lymphoma (ALCL). Data from the International T-cell Lymphoma Project reveals that ALK-positive ALCL has the best survival outcomes, while other PTCL subtypes, like ATLL, show poor prognosis. The introduction of brentuximab vedotin has improved outcomes for relapsed ALCL, though its effectiveness in other PTCL forms remains unclear. While CHOP remains standard therapy for PTCL, there is ongoing debate about combining brentuximab with etoposide and the role of stem cell transplants. Additionally, certain PTCL subtypes are more common in regions with endemic viral infections, complicating treatment approaches.

Ashwath Gurumurthi, M.D.
Advanced Lymphoma Fellow
Memorial Sloan Kettering Cancer Center