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As one of just two NCI-designated Comprehensive Cancer Centers in Virginia, VCU Massey Comprehensive 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 September and October 2023.

PUBLISHED RESEARCH

Blocking proteins could pull the plug on power for colon tumors

Massey research member: Can Senkal, Ph.D.
Journal: Cell Reports
Publication date: Sept. 8, 2023

A team of scientists at Massey discovered a previously-unknown interaction between proteins that is responsible for supplying energy to tumor cells and could hold significant implications for the development of future treatments for colon cancer. “This study is really exciting because we may be able to use these findings to inform the development of an entirely new cancer drug right here at Massey,” Senkal said.

VCU collaborators: Rowan Boyd, Sachin Kempelingaiah, Saurav Majumder, Ph.D., Grace Mavodza, Ph.D., Johnny Stiban, Ph.D., and Alexandra Straus

Implementation of a cancer education program in rural counties with the lowest HPV vaccination rates and health rankings

Massey research members: Michael Preston, Ph.D., and Vanessa Sheppard, Ph.D.
Journal: Journal of Health Research
Publication date: Sept. 14, 2023

Human papillomavirus (HPV) is the most commonly sexually transmitted infection. The Schooling Cancer Program was developed in partnership with a rural county public school district in Virginia to raise awareness about cancer risk factors, including HPV-related cancers and HPV prevention methods. Through this initiative, students learned essential health concepts and HPV-related risk factors.

VCU collaborators: Sarah Arezo, Charlotte Garrett, R.N., Shillpa Naavaal, B.D.S., M.S., M.P.H., and Marcie Wright, Ph.D., M.P.H.

Study pinpoints treatment targets for disrupting HPV viral life cycle

Massey research member: Iain Morgan, Ph.D.
Journal: Journal of Virology
Publication date: Sept. 15, 2023

Human papillomavirus 16 (HPV16) is a causative agent in around 3–4% of all human cancers, and currently, there are no anti-viral therapeutics available for combating this disease burden. During the HPV16 life cycle, the E2 protein binds simultaneously to the viral genome and host chromatin throughout mitosis, ensuring viral genomes reside in daughter cell nuclei following cell division. A new study enhances the understanding of a critical part of the HPV16 life cycle and presents several therapeutic targets for disruption of the viral life cycle.

VCU collaborators: Apurva Prabhakar, Ph.D., Molly Bristol, Ph.D., Aanchal Dubey, Christian Fontan, Ronald Hill, Claire James, Ph.D., Raymonde Otoa, Xu Wang and Calvin Yeager

Dual targeting of the PDZ1 and PDZ2 domains of MDA-9/Syntenin inhibits melanoma metastasis

Massey research members: Paul Fisher, M.Ph., Ph.D., FNAI, Umesh Desai, Ph.D., Nitai Mukhopadhyay, Ph.D., Devanand Sarkar, MBBS, Ph.D., and Xiang-Yang (Shawn) Wang, Ph.D.
Journal: Molecular Cancer Therapeutics
Publication date: Sept. 18, 2023

Genome-wide gene expression analysis and animal modeling indicate that the gene MDA-9/Syntenin positively regulates the spread of melanoma. Results from this study support the feasibility of engineering MDA-9 dual-PDZ inhibitors with enhanced antimetastatic activities and applications of IVMT-Rx-3 for developing novel treatment strategies effectively targeting melanoma, and potentially a broad spectrum of human cancers in which this gene is also overexpressed.

VCU collaborators: Swadesh Das, Ph.D., Anjan Pradhan, Daniel Afosah, Praveen Bhoopathi, Luni Emdad, M.B.B.S., Ph.D., Chunqing Guo, Ph.D., Amit Kumar, Ph.D., Padmanabhan Mannangatti, Ph.D., Mark Mochel, M.D., and Jinkal Modi

Scientists identify potential treatment strategy in triple-negative breast cancer

Massey research members: Senthil Radhakrishnan, Ph.D., and J. Chuck Harrell, Ph.D.
Journal: Scientific Reports
Publication date: Sept. 22, 2023

Proteasomes are a complex of proteins that support tumor growth, and their inhibition has been identified as an effective therapeutic strategy in breast cancer. Recent findings suggest that triple-negative breast cancer is particularly vulnerable to proteasome inhibition, and targeting the transcription factor NRF1 is a viable strategy for increasing the efficacy of proteasome inhibitors in this subtype of disease.

VCU collaborators: Holly Byers, Amy Brooks, Charles Clevenger, M.D., Ph.D., Alex Feygin, Jacqueline Grible, Ph.D., and Janakiram Vangala

Researchers identify potential driver of breast cancer disparity

Massey research members: Victoria Findlay, Ph.D., and David Turner, Ph.D.
Journal: Frontiers in Immunology
Publication date: Sept. 25, 2023

In the U.S., despite the recent decline in breast cancer deaths, Black women have a 41% higher death rate than white women. The protein Cav1 serves as a novel biomarker for poor outcomes in breast cancer. Through a study, researchers suggest the regulation of Cav1 by a molecule overexpressed in tumor cells (miR-510-5p) is a novel mechanism of aggressive disease growth and may be a driver of breast cancer disparities.

VCU collaborators: Gurbani Jolly and Bradley Krisanits, Ph.D.

Physical activity and sitting time important for managing symptoms in breast cancer survivors

Massey research members: Alexander Lucas, Ph.D., Vanessa Sheppard, Ph.D., Autumn Lanoye, Ph.D., Jessica LaRose, Ph.D., and Arnethea Sutton, Ph.D.
Journal: Cancer Medicine
Publication date: Sept. 28, 2023

Adjuvant endocrine therapy (AET) often causes debilitating endocrine symptoms that compromise quality of life in women diagnosed with hormone receptor-positive breast cancer. Through a recent study, researchers examined whether greater levels of physical activity or prolonged sitting were associated with reduced or worsened side effects of AET. Their findings suggest that both physical activity and sitting time were important with respect to managing symptoms and maintaining quality of life among breast cancer survivors.

VCU collaborators: Youngdeok Kim, Ph.D., R. Lee Franco, Ph.D., and Masey Ross, M.D.

Behavioral therapy for insomnia effective in brain cancer patients

Massey research members: Ashlee Loughan, Ph.D., and Autumn Lanoye, Ph.D.
Journal: Neuro-Oncology
Publication date: Oct. 5, 2023

Cognitive Behavioral Therapy for Insomnia (CBT-I), the front-line treatment for insomnia, has yet to be evaluated among patients with primary brain tumors despite high prevalence of sleep disturbance in this population. A new study found that telehealth group CBT-I is safe, feasible and acceptable among brain cancer patients, providing support for future randomized controlled pilot trials.

VCU collaborators: Youngdeok Kim, Ph.D., Amber Fox, and Kelcie Willis, M.S.

Implementing dietary strategies during puberty could help reduce breast cancer risk

Massey research members: Victoria Findlay, Ph.D., and David Turner, Ph.D.
Journal: Breast Cancer Research
Publication date: Oct. 6, 2023

Increased levels of advanced glycation end products (AGEs) — reactive metabolites linked with modern dietary patterns — are associated with increased breast cancer risk, however their significance has been largely overlooked due to a lack of direct cause-and-effect relationship. A recent study observed a disruption in mammary gland development in diets high in AGEs. The study suggests that implementing educational, interventional and pharmacological strategies during puberty to reduce AGEs associated with diet may be viewed as novel preventive and/or therapeutic initiatives for breast cancer.

VCU collaborators: Jackson Lane and Gowtami Panguluri

Fatty acids and fiber boost cardiac function in cancer survivors

Massey research members: W. Gregory Hundley, M.D., Dipankar Bandyopadhyay, Ph.D., Jennifer Jordan, Ph.D., Jessica LaRose, Ph.D., and Fadi Salloum, Ph.D.
Journal: Progress in Cardiovascular Diseases
Publication date: Oct. 16, 2023

Cancer therapies often cause cardiac injury and increase cardiovascular disease (CVD) risk. In non-cancer populations, higher diet quality is associated with protection against CVD, but the relationship between diet and cardiac function in cancer survivors is unknown. Through a recent study, researchers determined that greater consumption of unsaturated fatty acids and fiber was associated with favorable cardiac function in cancer survivors, while higher sugar intake was associated with worse cardiac function.

VCU collaborators: Moriah Bellissimo, Ph.D., R.D., Salvatore Carbone, Ph.D., and Jian He, M.S.

Niraparib and dostarlimab for the treatment of recurrent platinum-resistant ovarian cancer: results of a phase 2 study

Massey research member: Leslie Randall, M.D.
Journal: Gynecologic Oncology
Publication date: Oct. 25, 2023

This study assessed the efficacy, safety and health-related quality of life of a treatment regimen including dostarlimab combined with niraparib in patients with BRCA wild type recurrent platinum-resistant ovarian cancer who had previously received bevacizumab treatment. The study was terminated due to a low objective response rate observed for patients receiving this combination treatment. The finding highlights the difficulty in treating patients with this subset of ovarian cancer and underscores the need for effective therapies in this population.

Cardiovascular impact of near complete estrogen deprivation in premenopausal women with breast cancer

Massey research members: Jennifer Jordan, Ph.D., Wendy Bottinor, M.D., Mary Helen Hackney, M.D., and W. Gregory Hundley, M.D.
Journal: American Heart Journal
Publication date: Oct. 26, 2023

This journal outlines the design and implementation of the CROWN Study, which seeks to understand the natural history of women embarking on near-complete estrogen deprivation therapy to lower the risk of breast cancer recurrence. In studying myocardial blood flow during stress, as well as coronary plaque in these premenopausal patients, the researchers seek to identify cardiovascular flags that could be warning signs before cardiovascular events occur. Complete results of CROWN are anticipated in 2026-2027, though some information will be available earlier.

PUBLISHED REVIEWS

The cytoprotective role of autophagy in response to BRAF-targeted therapies

Massey research member: David Gewirtz, Ph.D.
Journal: International Journal of Molecular Sciences
Publication date: Sept. 30, 2023

BRAF-targeted therapies are widely used for the treatment of melanoma patients with BRAF V600 mutations. Vemurafenib, dabrafenib and encorafenib have demonstrated substantial therapeutic activity; however, the frequent development of resistance limits their efficacy. This review of the scientific literature relating to the role of autophagy that is induced in response to BRAF-inhibitors supports the premise that autophagy targeting or modulation could be an effective adjuvant therapy.

VCU collaborator: Ahmed Elshazly

Making the case for autophagy inhibition as a therapeutic strategy in combination with androgen-targeted therapies in prostate cancer

Massey research member: David Gewirtz, Ph.D.
Journal: Cancers
Publication date: Oct. 18, 2023

This paper is one in a series of articles that investigates the functional forms of autophagy induced in tumor cells in response to various chemotherapeutic modalities, with the overarching goal of determining whether autophagy targeting or modulation could serve as an effective adjuvant therapy. In this review, the researchers focused on androgen-targeted therapies in prostate cancer, including androgen biosynthesis inhibitors and androgen receptor antagonists.

VCU collaborator: Ahmed Elshazly

Written by: Blake Belden