Each year, the Molecular Therapeutics (MT) Research Program at Karmanos Cancer Institute honors the outstanding science of the program research members. At the 2022 annual symposium for MT in May, the inaugural “Top Paper” awards were presented in two categories: clinical science and basic science.
Hirva Mamdani, M.D., leader of the Thoracic Oncology Multidisciplinary Team, member of the Phase I Clinical-Pharmacology Program and director of the Lung Cancer Screening Program at Karmanos, as well as assistant professor of oncology at Wayne State University’s School of Medicine (WSU), was awarded the Top Clinical Science Paper Award. Yubin Ge, Ph.D., associate professor of oncology at WSU, received the Top Basic Science Paper Award.
The MT program advisory committee and program co-leaders selected the awardees from the best papers published in the previous 12 months. Criteria included the impact of the journal, the clinical impact of the research and its relevance to Karmanos’ mission as a National Cancer Institute-designated comprehensive cancer center.
“We created the award to recognize the immense contributions of researchers within the MT program,” said Asfar Azmi, Ph.D., leader of the Molecular Therapeutics Research Program, director of the Pancreas Cancer Research Initiative at Karmanos and associate professor in the Department of Oncology at WSU. “We received more than 20 entries for the award. The work of our two honorees highlights important discoveries that may benefit patients down the line.”
MT researchers identify new molecules, targets and strategies for treating cancer. The program integrates basic and translational scientists (working on drug development, new or established therapeutic targets or pathways, and cellular and genetic cancer biomarkers) with physicians conducting clinical trials at Karmanos.
“The MT program has more than 40 scientific members and more than 60 associate members,” Dr. Azmi said. “We have hundreds of studies and research programs underway at any time.”
Dr. Mamdani’s Awarded Research
Dr. Mamdani was the lead investigator and author of “A Phase II Trial of Adjuvant Durvalumab Following Trimodality Therapy for Locally Advanced Esophageal and Gastroesophageal Junction Adenocarcinoma: A Big Ten Cancer Research Consortium Study,” published in the September 2021 issue of Frontiers in Oncology.
Her research focused on a subgroup of patients with locally advanced esophageal cancer with a high relapse rate (75 percent) within the first year following chemotherapy, radiation therapy and surgical resection.
“We introduced a new modality on top of standard care: immunotherapy,” Dr. Mamdani said. “In this Phase II study, we used an immunotherapy drug called Durvalumab in the form of an infusion. Patients received this infusion once every four weeks for up to 12 months. In our study, 74 percent of patients remained relapse-free after one year. Most patients tolerated treatment fairly well. We were the first to report that immunotherapy could potentially be used to improve outcomes for these patients.”
A subsequent Phase III trial conducted across 117 medical centers using a different drug with the exact mechanism of action indicated the same benefit rate as Dr. Mamdani’s Phase II trial.
“This treatment is now a standard of care,” Dr. Mamdani said. “The bottom line – immunotherapy is a powerful tool for prolonging patient survival and leading to cures.”
“The MT program puts out many high-quality papers. I’m honored to be chosen for this award. It also acknowledges the time and effort we put into our studies. All the work done in MT is about pursuing new ideas in oncology to benefit patients.”
Dr. Ge’s Awarded Research
Dr. Ge received his award for “The combination of CUDC-907 and gilteritinib shows promising in vitro and in vivo antileukemic activity against FLT3-ITD AML,” published in the June 2021 issue of Blood Cancer Journal. Dr. Ge designed the study and was the lead researcher.
The research focused on acute myeloid leukemia (AML) patients with FLT3-ITD gene mutations. These patients have a lower rate of complete remission, shorter duration of complete remission, and much higher relapse rate when treated with the current chemotherapy. Thus, there is an urgent need of new therapies for this group of patients.
“In a previous study, I focused on a drug that is a specific inhibiter for FLT3,” Dr. Ge explained. “In 2018, the FDA approved a new drug called Gilteritinib for patients who relapse from standard chemotherapy. This drug was effective but only prolonged survival for 6 to 10 months. In another study, we demonstrated that a novel PI3K and HDAC dual inhibitor, CUDC-907, suppressed FLT3 in AML cells. Based on this finding, we hypothesized that if we combined the two drugs, we would see synergistic (1+1>2) antileukemic activity against pre-clinical models of AML with FLT3-ITD mutations.”
In-vitro studies showed the two drugs synergized to kill FLT3-mutated AML cells. Subsequent testing on an AML xenograft model in immunocompromised mice provided encouraging survival data.
“The mice tolerated the drugs well and only two out of six Gilteritinib plus CUDC-907 treated mice died after 190 days post cell injection into the mice,” Dr. Ge said. “We hope to design a clinical trial at Karmanos for relapsed and refractory FLT3-mutated AML patients.”
“I’m excited and honored to receive this recognition from MT program leadership. The awards reflect the excellence of our program and our research from the basic science and clinical side.”
For more information about molecular therapeutics research at Karmanos, visit the Molecular Therapeutics web page. Learn more about the clinical research partnership with Wayne State University School of Medicine here.