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As one of just two NCI-designated Comprehensive Cancer Centers in Virginia, VCU Massey Cancer Center is at the forefront of the nation’s cancer research efforts. Researchers at Massey conduct laboratory-based basic, population, and clinical and translational-focused research to advance improved approaches to prevent, diagnose and treat cancer. Continue reading to learn more about publications from Massey researchers in July and August 2023.

PUBLISHED RESEARCH

Study finds younger kidney cancer survivors at significant risk for heart problems

Massey research members: Wendy Bottinor, M.D., and W. Greg Hundley, M.D.
Journal: Journal of the National Comprehensive Cancer Network
Publication date: July 2023

New research out of Massey indicates that many adolescent and young adult (AYA) kidney cancer survivors are at a significantly elevated risk for heart issues. A study assessed the incidence and risk of hypertension — high blood pressure — and heart failure among AYA patients diagnosed with kidney cancer who also received a form of drug that blocks blood vessel growth as part of their treatment. In particular, the researchers looked at the effects of two drugs called sunitinib and sorafenib. They found that approximately half of AYAs treated with sorafenib and one-third of AYAs treated with sunitinib eventually developed hypertension.

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Immunotherapy leads to complete response in kidney cancer patient

Massey research member: Asit Paul, M.D., Ph.D.
Journal: International Journal of Surgical Pathology
Publication date: July 6, 2023

Numerous subtypes of kidney cancer have been identified by clinical researchers over recent years, prompting a need for novel treatment options for individualized forms of the disease. For one type of kidney cancer known as TFEB-amplified renal cell carcinoma, a specific type of immunotherapy targeting the protein PD-L1 has shown promise. Through a recent case report, a patient with advanced kidney cancer experienced a long-term, complete response to PD-L1-directed therapy.

VCU collaborators: Steven Christopher Smith, M.D., Ph.D., and Jinxing Yu, M.D., M.S.

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New care models needed to manage high blood sugar in cancer patients

Massey research members: Teresa Salgado, Ph.D., and Vanessa Sheppard, Ph.D.
Journal: Supportive Care in Cancer
Publication date: July 8, 2023

Hyperglycemia — high blood sugar — is a frequent complication of chemotherapy, occurring in 20–60% of patients. A recent study set out to assess oncologists’ responsibility, comfort and knowledge managing hyperglycemia in patients undergoing chemotherapy. The researchers determined that oncologists expected endocrinology or primary care clinicians to manage hyperglycemia during chemotherapy, and long wait times were among the top barriers cited when referring patients. The study authors suggest that new models of care delivery are needed to provide prompt and coordinated care for cancer patients experiencing hyperglycemia.

VCU collaborators: Dave Dixon, Pharm. D., Trang Le, M.D., Rotana Radwan, Pharm. D., and Erin Hickey Zacholski, Pharm. D.

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Study could inform the understanding of exercise intolerance in cancer survivors

Massey research members: W. Greg Hundley, M.D., Jennifer Jordan, Ph.D., and John McCarty, M.D.
Journal: Cardio-Oncology
Publication date: July 10, 2023

Cancer survivors often experience reduced exercise capacity and increased fatigue. Through a feasibility study, it was determined that a combination of cardiopulmonary exercise testing and stress cardiac magnetic resonance could be an effective strategy to measure oxygen levels in cancer survivors and help offer insights into the reasons for exercise intolerance in survivors experiencing fatigue.

VCU collaborators: Justin Canada, Ph.D., Antonio Abbate, M.D., Ph.D., Kevin DeCamp, Virginia McGhee, Rachel Myers, Mary Ann Reynolds, Katey Sweat, Cory Trankle, M.D., and Josh West

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GBA regulates EMT/MET and chemoresistance in skin cancer cells by modulating the cellular glycosphingolipid profile

Massey research member: Santiago Lima, Ph.D.
Journal: Cells
Publication date: July 18, 2023

Glycosphingolipids (GSL) are plasma membrane components that influence molecular processes involved in cancer initiation, progression and therapeutic responses. Therefore, understanding the mechanisms that regulate GSLs in cancer has important therapeutic potential. Through a recent study, researchers identified a potential strategy to overcome resistance to chemotherapy in skin cancer and other tumors.

VCU collaborators: Laura Clark and Amanda Dickinson, Ph.D.

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Scientists investigate role of immune cells in liver cancer

Massey research members: Masoud Manjili, Ph.D., DVM, Arun Sanyal, M.D., and Michael Idowu, M.P.H., MBBS
Journal: Scientific Reports
Publication date: August 3, 2023

Liver cancer is one of the leading causes of cancer death worldwide, and there is not a curative immunotherapy that exists for hepatocellular carcinoma, the most common form of liver cancer. This is partly due to the fact that not much is understood with regard to the collective function of the liver's immune system. Massey researchers collaborated on a study that identified a direct role of immune cells in the progression of liver disease and could inform future treatment interventions.

VCU collaborators: Nicholas Koelsch, Faridoddin Mirshahi, Amy Olex, Ph.D., and Mulugeta Saneshaw

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BRD4 inhibition as a strategy to prolong treatment response in breast cancer

Massey research members: David Gewirtz, Ph.D., and Hisashi Harada, Ph.D.
Journal: Cancers
Publication date: August 11, 2023

The combination of CDK4/6 inhibitors and fulvestrant or tamoxifen effectively prolongs survival in patients with estrogen receptor-positive (ER+) breast cancer. However, in the case of residual and metastatic disease, morbidity and mortality are virtually inevitable. A recent study evaluated the capacity of BET inhibitors to improve the response to standard-of-care treatment in ER+ breast cancer.

VCU collaborators: Ahmed Elshazly, Muruj Alshehri, Eesha Chakraborty, Victoria Neely and Melanie Sinanian

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Shortened course of treatment could reduce toxicity in leukemia

Massey research members: Keri Maher, D.O., Steven Grant, M.D., and Nolan Wages, Ph.D.
Journal: Leukemia Research
Publication date: August 16, 2023

Venetoclax, a small molecule BCL2 inhibitor, has revolutionized the treatment of acute myeloid leukemia (AML). Although traditionally dosed in 28-day cycles, new evidence suggests that shorter durations of venetoclax may have similar efficacy and improved tolerance. A new study suggests that an abbreviated regimen of venetoclax is a viable treatment strategy to reduce high-grade toxicity in AML patients.

VCU collaborators: Ian Bouligny, M.D., Yanal Alnimer, M.D., Josh Boron, Michael Doyel, Juhi Gor, M.D., Yiwei Hang, Thuy Ho, M.D., Graeme Murray, Tilak Patel, M.D., Valerie Tran, Chad Venn, Pharm. D., and Kyle Zacholski, Pharm. D.

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Targeting oncogenic mutant p53 and BCL-2 for small cell lung cancer treatment

Massey research members: Hisashi Harada, Ph.D., Sumitra Deb, Ph.D., Anthony Faber, Ph.D., and Jennifer Koblinski, Ph.D.
Journal: International Journal of Molecular Sciences
Publication date: August 23, 2023

Through a unique genomics and drug screening platform with approximately 800 solid tumor cell lines, a group of scientists found a subset of small cell lung cancer (SCLC) cell lines are hypersensitive to venetoclax, an FDA-approved inhibitor of BCL-2. Through a recent study, they developed a venetoclax-based combination with the HSP90 inhibitor, ganetespib, that targets Onc-p53 in subtypes of SCLC. They determined that simultaneously targeting BCL-2 and Onc-p53 by the combination of venetoclax and HSP90 inhibitors could be a promising approach for SCLC treatment.

VCU collaborators: Victoria Neely, Krista Dalton, Bin Hu, Ph.D., Alekhya Manchikalapud and Khanh Nguyen

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Researchers identify potential contributor to racial disparity in liver cancer

Massey research members: Devanand Sarkar, MBBS, Ph.D., and Mikhail Dozmorov, Ph.D.
Journal: Cancers
Publication date: August 27, 2023

Hepatocellular carcinoma (HCC) is the most common primary liver cancer arising from the liver cells. Black HCC patients have increased incidence and lower survival rates compared to non-Hispanic white patients. Through global gene expression analysis, scientists identified the activation of a key inflammatory pathway in liver cancer tumors in Black patients. They suggest that Black HCC patients might benefit from a holistic dietary approach, including ginger extract.

VCU collaborators: Saranya Chidambaranathan Reghupaty, Eva Davis and Rachel Mendoza

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PUBLISHED REVIEWS

From reductionistic approach to systems immunology approach for the understanding of tumor microenvironment

Massey research member: Masoud Manjili, Ph.D., DVM
Journal: International Journal of Molecular Sciences
Publication date: July 28, 2023

The tumor microenvironment (TME) is a complex and dynamic ecosystem that includes a variety of immune cells mutually interacting with tumor cells, structural/stromal cells and each other. This essay discusses how a systems immunology approach could revolutionize the scientific understanding of the TME by suggesting that internetwork interactions of the immune cell types create distinct collective functions independent of the function of each cellular constituent.

VCU collaborator: Nicholas Koelsch

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Cytoprotective, cytotoxic and cytostatic roles of autophagy in response to BET inhibitors

Massey research member: David Gewirtz, Ph.D.
Journal: International Journal of Molecular Sciences
Publication date: August 11, 2023

This review provides an overview of the cytoprotective, cytotoxic and cytostatic functions of autophagy in response to BET inhibitors in various tumor models in an effort to determine whether autophagy targeting or modulation could represent an effective therapeutic strategy to enhance the response to these modalities and also potentially overcome resistance to BET inhibition. 

VCU collaborator: Ahmed Elshazly

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Written by: Blake Belden