The Board of Directors of Brandon’s Foundation recently announced its 2017 research grant awardees. Nira Ben-Jonathan, PhD, Professor of Cancer Biology, University of Cincinnati (UC), Ohio is the recipient of a $20,000 grant to investigate Novel Treatments for Head and Neck Cancer using FDA-approved Drugs. Wendi O’Neill, DDS, The Ohio State University (OSU), Department of Otolaryngology-Head & Neck Surgery received a $15,000 grant to study A Novel Immunotherapy Combination for Improved Head and Neck Cancer Outcomes. A third grant of $10,000 was awarded to Tammara L. Watts, MD, PhD, Assistant Professor, The University of Texas Medical Branch (UTMB), Department of Otolaryngology to study Crenolanib: Targeting the Tumor Microenvironment in Oral Cavity and Oropharyngeal Squamous Cell Carcinoma.

Twenty-four research proposals were submitted in response to the Foundation’s Request for Proposals (RFP) in March 2017. The Foundation’s Board depends on the reviews of project proposals by experts in the field of head and neck cancer to determine which projects show the most promise and best “fit” the Foundation goals. The Board is very grateful to these reviewers, who give generously of their valuable time to help with this process. Thank you to 2017 reviewers:

William Barrett, MD – University of Cincinnati

Mihir K. Bhayani, MD – University of Chicago

Keith A. Casper, MD – University of Michigan

Brenda Diergaarde, PhD, University of Pittsburgh

Michael Gibson, MD, PhD – Vanderbilt University

Stephen Lai, MD, PhD – MD Anderson

Tahir Latif, MD. MBA – University of Cincinnati

Carol Lewis, MD, MPH – MD Anderson

Michelle L. Mierzwa, MD – University of Michigan

Yash J. Patil, MD – University of Cincinnati

Jack Phan, MD, PhD – MD Anderson

Curtis R. Pickering, PhD – MD Anderson

Timothy D. Struve, MD – University of Cincinnati

Shirley Yu Su, MD – MD Anderson

Vinita Takiar, MD, PhD – University of Cincinnati

Eric Thorpe, MD – Loyola (Chicago)

Keith Wilson, MD – University of Cincinnati

Trisha Wise-Draper, MD, PhD -- University of Cincinnati

(Several additional reviewers preferred to remain anonymous.)

Summary of Funded Proposals

Novel Treatments for Head and Neck Cancer using FDA-approved Drugs (Nira Ben-Jonathan, PhD, UC)

Patients with head and neck cancer (HNC) are commonly treated with surgery, radiation, and/or conventional chemotherapeutic drugs such as cisplatin and taxol. However, all these treatments are associated with debilitating side effects, and a significant decrease in the quality of life. Moreover, treatment failure due to loss of drug responsiveness are common. Consequently, there is an urgent need for alternative, more targeted therapies for this disease. Our laboratory discovered that dopamine, a small molecule best known for its role in brain functions, is also involved in HNC. Activation of specific dopamine receptors, named D1R, located on the surface of cancer cells, suppressed cell growth and increased the ability of conventional anti-cancer drugs to kill the cells. The first objective is to determine the relative occurrence of D1R in several hundred pathological tumor samples, and correlate D1R presence with advance disease stage, responsiveness to treatment, and overall patient survival. The second objective is to use four dopamine/D1R-associated drugs, which are already approved by the FDA to treat unrelated health conditions. HNC cells will be incubated with each anti-D1R drug, alone or together, with cisplatin or taxol, and cell growth/death will be determined. We predict that a combination treatment will be highly beneficial as a future treatment for HNC patients, as it should markedly decrease the severe side effects of conventional chemotherapeutic drugs while increasing the overall efficacy of tumor-suppression.     

A Novel Immunotherapy Combination for Improved Head and Neck Cancer Outcomes (Wendi O’Neill, DDS, OSU)

Despite improved treatment outcomes for many cancer types, little progress has been made in the management of poorly differentiated head and neck cancer (HNC). Our work aims to improve patient outcomes by combining two promising therapeutic strategies targeting PD1 and HIF. Each plays distinct and important roles in cancer, yet there is established regulatory interplay between them. Inhibiting these key players together makes an intriguing and rational therapeutic strategy. We anticipate that our novel combination of HIF and PD-1 inhibitors will achieve superior anti-cancer activity compared to either agent alone. Our work, if successful, will provide the needed evidence to design and initiate a clinical trial to assess the activity of our novel therapeutic combination in patients with poorly differentiated HNC.

Crenolanib: Targeting the Tumor Microenvironment in Oral Cavity and Oropharyngeal Squamous Cell Carcinoma (Tammara L. Watts, MD, PhD, UTMB)

Treatment costs for patients with head and neck cancer exceed $3 billion annually. Treatment failures give rise to recurrent and/or persistent disease often associated with concomitant resistance to chemo- and radiotherapy. The clinical behavior observed by head and neck surgeons, like myself, suggests that therapies aimed at solely targeting cancer cells are inadequate and that new treatment modalities are urgently needed. Mesenchymal stem cells (MSCs), and other non-cancerous cells form a dense tumor associated microenvironment around the cancer cells, and are known to be critical contributors to the growth of several solid tumors. This dense tumor microenvironment (TME) is pathognomonic for patients with oral cavity (OC)- and oropharyngeal (OP) squamous cell carcinoma (SCC). Our central hypothesis is that treatment failures and local regional recurrence in OC- and OPSCC is derived, at least in part, from the presence of TME MSCs.  Therefore,disruption of MSC chemotaxis to the TME may inhibit the effects of MSCs, namely on the proliferation of cancer stem cells (CSCs) and cancer associated fibroblasts (CAFs) in the TME, thereby improving tumor cell responsiveness to conventional treatments such as chemotherapy and radiation. The monies from this grant will be used to fund the in vivo (mouse) studies to determine the effect of stem cells on tumor development and metastasis in OC cancer. 

Thank you for your continued support!

Congratulations to the 2017 grant award recipients! Thank You, reviewers! And a HUGE Thank You to all who donate to Brandon’s Foundation via the web site Donate page (directly or mail in), participate in the Mardi Gras MASKerade, host and attend events that benefit the foundation, such as Great Food for a Great Cause and MCA Day Chicago (see Past Events), etc.! In the last four years Brandon’s foundation has awarded more than $140,000 to fund innovative head and neck cancer research projects. None of this would be possible without your continued contributions. Thank you!