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March/April 2023: Published research at Massey

May 15, 2023

Facade of VCU Massey Cancer Center's Goodwin Research Laboratory

As one of just two NCI-designated 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 March and April 2023.

PUBLISHED RESEARCH:

Phase 1 study of belinostat and adavosertib in patients with relapsed or refractory myeloid malignancies

Massey research members: Steven Grant, M.D., and Dipankar Bandyopadhyay, Ph.D.
Journal: Cancer Chemotherapy and Pharmacology
Publication date: March 2, 2023

Belinostat is an intravenous histone deacetylase inhibitor approved for the treatment of T-cell lymphomas, and adavosertib is an oral Wee1 inhibitor. Preclinical studies of the combination therapy demonstrated synergy in human acute myeloid leukemia (AML) lines as well as AML xenograft mouse models. Massey researchers concluded that the combination of belinostat and adavosertib at the tested dose levels was feasible, but without efficacy signals in the relapsed/refractory myelodysplastic syndrome/AML population.

VCU collaborators: Daniel Hudson, Maciej Kmieciak, Ph.D., Heidi Sankala, Ph.D., Ellen Shrader, R.N., Mary Beth Tombes, ACNP, and Caryn Weir, R.N.

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Scientists identify set of drugs that could be effective in breast cancer

Massey research members: Chuck Harrell, Ph.D., and Mikhail Dozmorov, Ph.D.
Journal: Cancers
Publication date: March 3, 2023

Basal-like breast cancers comprise the majority of triple-negative breast cancers (TNBC) and lack effective treatment options that have a sustained response. Harrell led a recent study that identified 20 potent drug combinations when paired with alpesilib in TNBC and formed a basis toward future clinical studies with these molecules.

VCU collaborators: Julia Altman, Mohammad Alzubi, Ph.D., David Boyd, Holly Byers, Andrea Ferreira-Gonzalez, Ph.D., Jacqueline Grible, Ph.D., Nicole Hairr, Tess Leftwich, Amy Olex, Ph.D., Scott Turner, Ph.D., Aaron Valentine and Emily Zboril.

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Elevated blood pressure common in young cancer survivors

Massey research members: Wendy Bottinor, M.D., Dipankar Bandyopadhyay, Ph.D., Jennifer Jordan, Ph.D., and Madhu Gowda, M.D.
Journal: Journal of the American College of Cardiology
Publication date: March 7, 2023

Hypertension is common among cancer survivors and is a leading modifiable risk factor for adverse cardiovascular outcomes in this population. Through a recent study, Massey researchers found that among a group of young adults previously treated with anthracyclines — a type of chemotherapy drug — over 25% were found to have elevated or hypertensive blood pressure. Recognition that blood pressure abnormalities may be common among young cancer survivors can allow for early detection and cardiovascular risk reduction.

VCU collaborators: Ericka Miller, David Chuquin, M.D., Xiaoyan Deng, M.S., Yiwei Hang, Sherin Menachery and Uyen Truong, M.D.

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Race impacts vaginal microbiome and HPV-related cancer

Massey research members: Katherine Tossas, Ph.D., Stephanie Sullivan, M.D., and Robert A. Winn, M.D.
Journal: Journal of Women’s Health
Publication date: March 10, 2023

The vaginal microbiome (VMB) plays an important role in the persistence of HPV infection and differs by race and among women with cervical dysplasia, a precancerous condition caused by HPV infection. Findings from a study led by Tossas suggest that race is a modifier of the VMB in the development of HPV-related cancers, and an optimal VMB does not appear to be protective for non-Latina Black women compared with non-Latina white women.

VCU collaborators: Gregory Buck, Ph.D., Robert Perera, Ph.D., Sadia Sayeed, M.D., Myrna Serrano, Ph.D., and Bin Zhu.

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Racial disparities exist in opioid use among breast cancer survivors

Massey research members: Sunny Jung Kim, Ph.D., Vanessa Sheppard, Ph.D., Dipankar Bandyopadhyay, Ph.D., and Arnethea Sutton, Ph.D.
Journal: Cancer Medicine
Publication date: March 14, 2023

Pain is one of the prevalent health problems in cancer survivors, and opioids are often used as part of therapy for cancer-related pain. Massey researchers found that there are racial differences in opioid prescriptions supplied for pain management and symptomatic outcomes in breast cancer survivors. They suggest that further research is needed to understand the causes of these disparities.

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Disparities affect racial differences in use of surveillance mammography among breast cancer survivors

Massey research members: Vanessa Sheppard, Ph.D., Bassam Dahman, Ph.D., Sunny Jung Kim, Ph.D., and Kandace McGuire, M.D.
Journal: BMC Women’s Health
Publication date: March 30, 2023

Surveillance mammography is recommended annually for early detection of disease relapse among breast cancer survivors; yet Black women have poorer national rates of surveillance mammography compared to white women. A recent study from Massey researchers set out to understand the impact of socioeconomic disparities on racial differences in the use of surveillance mammography among breast cancer survivors. The researchers determined that Black women living in non-metropolitan counties are an important subgroup for future research and screening and navigation interventions.

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Scientists investigate treatment resistance in non-small cell lung cancer

Massey research members: Mario Acunzo, Ph.D., Howard Li, M.D., Patrick Nana-Sinkam, M.D.
Journal: Oncogene
Publication date: March 31, 2023

Lung cancer is the leading cause of cancer-related deaths in the United States, and tyrosine kinase inhibitors (TKIs) have become the standard of care for non-small cell lung cancer (NSCLC) patients harboring an EGFR mutation. Through a recent study, Massey researchers identified MET as a target for miR-411-5p editing in position 5 of the seed region. Given the role of MET in EGFR TKIs resistance, this study investigated the role of non-coding RNA editing on MET signaling, focusing on EGFR TKIs resistance in NSCLC. The results shed light on the potential importance of miRNA post-transcriptional modifications in drug response in cancer.

VCU collaborators: Giulia Romano, Ph.D., Patricia Le, Lavender Micalo, Michela Saviana and Daniel del Valle-Morales, Ph.D.

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Targeting an enzyme could prevent chemo-related kidney injury

Massey research members: Ningjun Li, M.D., and David Gewirtz, Ph.D.
Journal: Molecular Pharmacology
Publication date: April 1, 2023

Cisplatin is a potent chemotherapy used as a frontline treatment for many solid tumors, such as breast, ovarian, lung, testicular, and head and neck cancer. However, acute kidney injury is a common side effect of this therapy, which often hampers the continuation of cisplatin treatment. Recent experiments suggest that targeting the FAAH enzyme could provide a novel therapeutic strategy for preventing cisplatin-induced kidney injury.

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Muscle strain could signal cardiovascular risk in cancer survivors

Massey research members: Wendy Bottinor, M.D., and Dipankar Bandyopadhyay, Ph.D.
Journal: Cancers
Publication date: April 18, 2023

Cardiovascular disease is a leading contributor to mortality among childhood, adolescent and young adult cancer survivors. Through a recent analysis, Massey researchers examined the role of echocardiography-based myocardial strain in identifying survivors at risk for left ventricular dysfunction. They determined that longitudinal and circumferential muscle strain can likely aid the identification of survivors at risk for cardiovascular dysfunction and provide an opportunity for early intervention.

VCU collaborator: Xiaoyan Deng, M.S.

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PUBLISHED EDITORIALS:

Addressing disparities in cancer care and incorporating precision medicine for minority populations

Massey research member: Robert A. Winn, M.D.
Journal: Journal of the National Medical Association
Publication date: March 30, 2023

Continued progress toward equitable cancer outcomes will require expanding access to cancer prevention, early detection and treatment for all Americans. A recent editorial argued that precision medicine has the potential to improve health and offer a unique opportunity to bridge some of the longstanding racial gaps in health care and research. The authors state that further development of technology, novel treatments, population resources and sustained engagement with minority communities are critical to mitigate racial disparities.

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PUBLISHED REVIEWS:

The adaptation model of immunity: Signal IV matters most in determining the functional outcomes of immune responses

Massey research member: Masoud Manjili, Ph.D., D.V.M.
Journal: Journal of Immunology
Publication date: March 1, 2023

Current research in immunology and immunotherapy is fully influenced by the self–nonself model of immunity. This essay discusses current theoretical models of immunity, as well as their impacts and limitations, and expands on the adaptation model of immunity to galvanize a new direction for the treatment of autoimmune diseases, organ transplantation and cancer.

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Neighborhood deprivation, racial segregation and associations with cancer risk and outcomes across the cancer-control continuum

Massey research members: Bernard Fuemmeler, Ph.D., M.P.H., Robert A. Winn, M.D., Jie Shen, Ph.D., and Hua Zhao, Ph.D.
Journal: Molecular Psychiatry
Publication date: March 3, 2023

Racial and ethnic disparities in cancer incidence and outcome are partially due to the inequities in neighborhood advantage. Through an expert review, Massey researchers discussed some of the findings related to work on area-level neighborhood variables and cancer outcomes. They concluded that evidence supports the notion that neighborhood deprivation and racial segregation have unfavorable impacts on cancer.

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PI3k inhibitors in NHL and CLL: An unfulfilled promise

Massey research member: Victor Yazbeck, M.D.
Journal: Blood and Lymphatic Cancer: Targets and Therapy
Publication date: March 8, 2023

The phosphatidylinositol-3 kinases (PI3K) pathway is overactivated in several malignancies, and developing small molecules targeting this pathway has long been of clinical interest for a plethora of neoplasms. A recent review examined possible ways that could benefit the successful development of PI3k inhibitors: one strategy that is gaining momentum is the adoption of intermittent dosing instead of continuous dosing. Considering their clinical efficacy, this review suggests that further investigations are needed to fully potentialize the benefit of PI3K inhibitors by improving their safety profiles in order to meet the needs of patients with indolent non-Hodgkin’s lymphoma and chronic lymphocytic leukemia.

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Paraneoplastic glomerulonephropathy associated with renal cell carcinoma: A descriptive analysis of published reports

Massey research member: Asit Paul, M.D., Ph.D.
Journal: Cureus
Publication date: March 30, 2023

Paraneoplastic glomerulonephropathy (PGN) is a rare paraneoplastic syndrome that is associated with a variety of malignancies. Patients with renal cell carcinomas (RCCs) often develop paraneoplastic syndromes, including PGN. A recent published review provides a descriptive analysis of the clinical presentation, treatment and outcomes of 35 published patient cases of PGN associated with RCCs over the past four decades in PubMed-indexed journals. The analysis demonstrates the importance of cancer-specific therapy; nephrectomy in localized disease and systemic therapy in metastatic disease, along with immunosuppression, was the most effective management of PGN.

VCU collaborators: Samina Hirani, M.D., and Jason Kidd, M.D.

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Written by: Blake Belden

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