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Fox Chase Graduate Student Billy Truong Recognized With ASH Abstract Achievement Award

December 13, 2021

Billy Truong, a doctoral candidate at Fox Chase Cancer CenterBilly Truong, a doctoral candidate at Fox Chase Cancer Center

PHILADELPHIA (December 13, 2021)—Billy Truong, a doctoral candidate at Fox Chase Cancer Center, was awarded the American Society of Hematology (ASH) Abstract Achievement Award for a poster that he presented at the 63rd ASH Annual Meeting and Exposition.

“Personally, I’m very grateful to be recognized by ASH, and more importantly, to be a part of this project, which addresses a critical gap in knowledge for MAP kinase-targeted therapy for myeloproliferative neoplasm treatment,” said Truong, who is working towards his degree in the lab of David Wiest, PhD, chief scientific officer and co-leader of the Blood Cell Development and Function Research Program.

“Much of the research effort in studying MAPK signaling in cancer has been thwarted by resistance and toxicity associated with targeting ERK, a kinase which is also very important for cell survival and immune responses. We believe that by targeting specific ERK binding substrates we can identify novel targets that are more pertinent to cancer progression while limiting cytotoxic effects,” he said.

Truong’s abstract is titled, “ERK2 Substrate Binding Domains Perform Opposing Roles in Pathogenesis of a JAK2V617F-Driven Myeloproliferative Neoplasm.” His study examines the interactions between the kinase ERK2 and the molecules it regulates. His work describes how these interactions are mediated by the common docking (CD) D-domain and the DEF-binding pocket (DBP) domain. 

ERK plays an important role in a variety of solid and blood malignancies, including myeloproliferative neoplasms (MPN), a collection of neoplasms that include polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF). JAK2-V617F is a cancer-causing mutation that is expressed in 95% of patients with PV and 40% to 50% of patients with ET and MF.

A good percentage of these patients become resistant to standard therapeutic treatment with the JAK1/2 inhibitor ruxolitinib. ERK is commonly activated in MPN cells in response to cytoreductive therapy, which is used to control the number of red and white blood cells and platelets in the body.

“By using genetic mouse models that selectively inactivated either the D or DEF domain of ERK2, we are able to demonstrate that ERK2-DBP domain opposes the progression of JAK2-V617F mediated myeloproliferative neoplasm. As a result of our findings on the ERK-DEF domain, we identified a compound, 76, which selectively blocks ERK2 action on D-domain substrates and attenuates MPN clone survival in vitro and in vivo,” he said.

Truong conducted the study with other researchers at Fox Chase—particularly physician-scientist Yong Zhang, MD, PhD, and research specialist Esteban Martinez—and the Fels Institute for Cancer Research and Molecular Biology at Temple University. Fox Chase is part of the Temple University Health System.

“We believe that this compound can be used as a tool to improve MAPK-targeted therapy not only for MPN but for all other cancers where RAS/MAPK signaling is constitutively activated. We are excited to see how different ERK binding modalities alter cancer signaling, which can lead to more efficacious strategies against resilient cancers,” he said.

“The advances that we made support a collective mission here at the center to discover and investigate novel strategies to target incurable cancers,” said Truong.

The Hospital of Fox Chase Cancer Center and its affiliates (collectively “Fox Chase Cancer Center”), a member of the Temple University Health System, is one of the leading cancer research and treatment centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence five consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship and community outreach. It is the policy of Fox Chase Cancer Center that there shall be no exclusion from, or participation in, and no one denied the benefits of, the delivery of quality medical care on the basis of race, ethnicity, religion, sexual orientation, gender, gender identity/expression, disability, age, ancestry, color, national origin, physical ability, level of education, or source of payment.

 

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