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January/February 2023: Published research at Massey

Mar 10, 2023

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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 January and February 2023.

PUBLISHED RESEARCH:

Synthetic compounds promote anticancer activity in colorectal tumors

Massey research members: Umesh Desai, Ph.D., and Bhaumik Patel, M.D.
Journal: Journal of Medicinal Chemistry
Publication date: Jan. 12, 2023

Glycosaminoglycans (GAGs) belong to a class of molecules that bind to proteins that have major functions in a number of diseases, including cancer; however, there are currently very few GAG-based drugs available, making them a rich resource for discovering new medicinal agents. Desai and Patel successfully used synthetic sulfated GAG mimetics to block tumor growth in colorectal cancer cells, and they established the paradigm that cholesterol derivatization of GAG mimetics offers an effective approach for administering these agents orally.

VCU collaborators: Elsamani Abdelfadiel, Daniel Afosah, Rio Boothello, Rawan Fayyad, Leopoldo Fernandez, M.D., Shravan Morla, Ph.D., Connor O’Hara, Ongolu Ravikumar, Syed Ammer Shah

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Drug combination shows potential in aggressive leukemia

Massey research member: Steven Grant, M.D.
Journal: Clinical Cancer Research
Publication date: Jan. 18, 2023

New research from Massey suggests that a novel type of combination therapy could offer key insights into future treatment strategies for acute myeloid leukemia (AML) patients. Through a recent study, Grant, the associate director for translational research at Massey, along with his collaborators determined that using a class of drugs known as dual mTORC1/2 inhibitors in combination with venetoclax dramatically suppressed the growth of a variety of human leukemic cell types, including cells taken from AML patients.

VCU collaborators: Sri Lakshmi Chalasani, Xiaoyan Hu, Ph.D., Maciej Kmieciak, Lin Li, Jewel Nkwocha, Kanika Sharma

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Class of drugs could improve metastatic breast cancer treatment

Massey research member: David Gewirtz, Ph.D.
Journal: Frontiers in Oncology
Publication date: Jan. 18, 2023

Through recent experiments, Gewirtz and his collaborators indicated that BET inhibitors/degraders may potentially improve standard-of-care therapy in metastatic ER-positive breast cancer patients and may further prolong progression-free survival.

VCU collaborators: Ahmed Elshazly, Ryan Finnegan, Nipa Patel, Tammy Tran, Liliya Tyutyunyk-Massey

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SRA inhibition improves antitumor potency of antigen-targeted chaperone vaccine

Massey research members: Chunqing Guo, Ph.D., Shawn Wang, Ph.D., Masoud Manjili, Ph.D.
Journal: Frontiers in Immunology
Publication date: Jan. 30, 2023

Previous research demonstrated that scavenger receptor A (SRA) acts as an immunosuppressive regulator of dendritic cell (DC) function in activating antitumor T cells. This study investigated the potential of inhibiting SRA activity to enhance DC-targeted chaperone vaccines, including one that was recently evaluated in melanoma patients. The research team found that short hairpin RNA-mediated SRA silencing significantly enhances the immunogenicity of DCs that have captured chaperone vaccines designed to target melanoma.

VCU collaborators: Jinyang Cai, Ph.D., Zheng Liu, Ph.D., Jie Qian, Ph.D., Xiaofei Yu, Ph.D.

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Novel mutant KRAS addiction signature predicts response to the combination of ERBB and MEK inhibitors in lung and pancreatic cancers

Massey research member: Said Sebti, Ph.D.
Journal: iScience
Publication date: Jan. 30, 2023

KRAS mutations are prevalent in pancreatic and lung cancers, but not all mutant KRAS tumors are addicted to mutant KRAS. This study discovered a 30-gene transcriptome signature “KDSE30” that encodes a novel EGFR/ERBB2-driven signaling network and predicts mutant KRAS, but not NRAS or HRAS, oncogene addiction.

VCU collaborators: Aslamuzzaman Kazi, Ph.D., Alok Ranjan, Ph.D., Katarzyna Tyc, Ph.D., Rui Wang, Ph.D.

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Advancing more equitable care with Health Equity Report Card

Massey research member: Robert A. Winn, M.D.
Journal: Journal of the National Comprehensive Cancer Network
Publication date: Feb. 2023

Cancer prevention and treatment systems are significantly impacted by interpersonal, organizational, structural and systemic racism. A wide body of research has found that racial disparities in both cancer care outcomes and access to guideline-concordant care are pervasive throughout the nation. Winn, the director at Massey, recently co-authored an article which highlights the efforts of the Elevating Cancer Equity Working Group to develop an actionable framework for organizational and clinical practice change to create more equitable systems of cancer care delivery through a Health Equity Report Card.

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Synergistic interactions between the hypomethylating agent thio-deoxycytidine and venetoclax in myelodysplastic syndrome cells

Massey research member: Steven Grant, M.D.
Journal: Hematology Reports
Publication date: Feb. 2, 2023

Myelodysplastic syndrome (MDS) represents a group of malignant disorders involving myeloid hematopoietic stem cells, which generally culminates in bone marrow failure and/or transformation to acute myeloid leukemia (AML). Interactions between the novel hypomethylating agent (HMA) thio-deoxycytidine (T-dCyd) and the BCL-2 antagonist ABT-199 (venetoclax) have previously been examined in human MDS cells. This study suggests that combining T-dCyd with ABT-199 kills MDS cells through an ROS-dependent mechanism, and the research team argues that this strategy warrants consideration in MDS therapy.

VCU collaborators: Xiaoyan Hu, Ph.D., Lin Li, Jewel Nkwocha, Kanika Sharma, Liang Zhou

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Sphingosine kinase 2 in stromal fibroblasts creates a hospitable tumor microenvironment in breast cancer

Massey research members: Sarah Spiegel, Ph.D., Mikhail Dozmorov, Ph.D., Christopher Green, Ph.D., Chunqing Guo, Ph.D., Shawn Wang, Ph.D.
Journal: Cancer Research
Publication date: Feb. 15, 2023

Reciprocal interactions between breast cancer cells and the tumor microenvironment are important for cancer progression and metastasis. This research demonstrated that the deletion or inhibition of sphingosine kinase 2, which produces sphingosine-1-phosphate, markedly suppresses syngeneic breast tumor growth and lung metastasis in mice by creating a hostile microenvironment for tumor growth and invasion.

VCU collaborators: Michael Maceyka, Ph.D., Melissa Maczis, Ph.D., Sheldon Milstein Elisa Palladino, Ph.D., Cynthia Weigel

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Cancer patient and caregiver communication about economic concerns and the effect on patient and caregiver partners’ perceptions of family functioning

Massey research member: Maria Thomson, Ph.D.
Journal: Journal of Cancer Survivorship
Publication date: Feb. 20, 2023

A cancer diagnosis can bring heightened emotional stress and financial strain for most cancer patients and their families. Thomson co-authored a study suggesting that efforts to address financial toxicity in cancer care should include examination of how patients and families communicate.

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Traditional eligibility criteria limits clinical trial participation

Massey research member: Jose Trevino, M.D.
Journal: JNCI Cancer Spectrum
Publication date: Feb. 21, 2023

Traditional clinical trial eligibility criteria restrict study populations, perpetuating enrollment disparities. Trevino and a team of collaborators set out to assess the implementation of modernized eligibility criteria guidelines among pancreatic cancer clinical trials in the U.S. They determined that overall compliance with modernized criteria remains poor and advocated for stakeholders to update protocols and scrutinize traditionally restrictive eligibility criteria.

VCU collaborators: Devon Freudenberger, M.D., and Vignesh Vudatha, M.D.

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Human Papillomavirus 16 E2 interaction with TopBP1 is required for E2 and viral genome stability during the viral life cycle

Massey research members: Iain Morgan, Ph.D., Molly Bristol, Ph.D.
Journal: Journal of Virology
Publication date: Feb. 22, 2023

Human papillomaviruses are pathogens that cause a host of diseases ranging from benign warts to cancers. This research demonstrates that HPV16 and HPV11 E2 protein expression is dependent upon TopBP1 interaction in keratinocytes interacting with fibroblasts, which recapitulate stromal interactions in culture. The study findings suggest that the CK2 inhibitor CX4945 could alleviate HPV11 disease burden.

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

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Protein partnership effectively fends off pancreatic cancer progression

Massey research member: Azeddine Atfi, Ph.D.
Journal: Journal of Cell Biology
Publication date: Feb. 24, 2023

Scientists at Massey uncovered a previously unrecognized relationship between two sets of proteins that operate in tandem to fend off the growth of pancreatic cancer. The findings could provide pivotal information for the development of novel therapies for what is currently an incurable disease. New research discovered that the simultaneous activation of two gene-regulating proteins, Prdm16 and Smad4, is associated with a cutback in pancreatic cancer progression.

VCU collaborators: Allyn Austin Bryan, Deanna Campbell, Creighton Friend, Eric Hurwitz, Ting-Xuan Lu, Thien Ly Nguyen, Parash Parajuli, Ph.D., and Steven Smith, M.D., Ph.D.

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PUBLISHED EDITORIALS:

Refining the competency-based assessment of radiation oncology medical residents

Massey research member: Emma Fields, M.D.
Journal: International Journal of Radiation Oncology, Biology, Physics
Publication date: Jan. 1, 2023

Graduate medical education is increasingly using a competency-based training assessment model, which requires individualized evaluations of trainees on specific domains of competence. Fields and her collaborators co-authored an editorial evaluating the Milestones program, a competency-based training assessment model for radiation oncology medical residents.

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Non-lymphoid functions of regulatory T cells in health and disease

Massey research member: Paula Bos, Ph.D.
Journal: Frontiers in Immunology
Publication date: Jan. 16, 2023

Over-exuberant immune response can be self-destructive and is required to be efficiently controlled to avoid collateral damage. Foxp3+ regulatory T (Treg) cells are a subtype of CD4+ lymphocytes that serve this paramount purpose through mechanisms of peripheral tolerance. This series of articles covers various aspects of the biology of Treg cells of non-lymphoid origin, with an overall goal of providing a comprehensive viewpoint of prominent researchers in the field.

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PUBLISHED REVIEWS:

Mechanisms of myeloid leukemogenesis: Current perspectives and therapeutic objectives

Massey research members: Steven Grant, M.D., Keri Maher, D.O.
Journal: Blood Reviews
Publication date: Jan. 2023

In this review, mechanisms contributing to myeloid leukemogenesis are summarized, highlighting aberrations of epigenetics, transcription factors, signal transduction, cell cycling and the bone marrow microenvironment. The mechanisms contributing to acute myeloid leukemia are detailed to spotlight recent findings that convey clinical impact.

VCU collaborator: Ian Bouligny, M.D.

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Is autophagy inhibition in combination with temozolomide a therapeutically viable strategy?

Massey research member: David Gewirtz, Ph.D.
Journal: Cells
Publication date: Feb. 7, 2023

Temozolomide is an oral alkylating agent that is used as the first-line treatment for glioblastoma multiform, and in recurrent anaplastic astrocytoma, as well as having demonstrable activity in patients with metastatic melanoma. In this review, the scientists explore the available literature and provide an overview of the evidence for the promotion of protective autophagy in response to temozolomide, highlighting the possibility of targeting autophagy as an adjuvant therapy to potentially increase the effectiveness of temozolomide and to overcome the development of resistance.

VCU collaborator: Ahmed Elshazly

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Written by: Blake Belden

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