The AACR-Pfizer Fellowships represent a joint effort to encourage and support postdoctoral or clinical research fellows to conduct cancer research and to establish a successful career path in this field. The research proposed for funding must have direct applicability to breast cancer or immuno-oncology research and may be basic, translational, clinical, or epidemiological in nature.
Scientific Statement of Research
Since breast cancer is a heterogenous disease, it is critical to discover novel drug targets to diversify the treatment spectrum. FTO is the first identified N6-methyladenosine RNA demethylase and has been shown to play a role in tumorigenesis in leukemia and brain tumors, but its function remains elusive in breast cancer. Dr. Tan’s preliminary data shows that FTO promotes proliferation of breast cancer cells and demonstrates the therapeutic potential of a novel FTO inhibitor in breast cancer. His proposal aims to identify FTO targets that are post-transcriptionally modulated by FTO using transcriptome-wide sequencing methods and to assess the efficacy of the FTO inhibitor using both in vitro and in vivo models of breast cancer.
Dr. Tan is currently a postdoctoral fellow in Dr. Jianjun Chen’s laboratory at the City of Hope Beckman Research Institute. His research focuses on how the N6-methyladenosine epitranscriptome influences tumorigenesis and on developing anti-tumor therapies that modulate the epitranscriptome. Dr. Tan completed his PhD in 2018 under the guidance of Dr. Shou-Jiang Gao at the University of Southern California, where he elucidated the role of N6-methyladenosine in Kaposi’s Sarcoma-associated herpesvirus replication and tumorigenesis. He obtained his MS and BS degrees from California State Polytechnic University, Pomona.
Acknowledgment of Support
The AACR-Pfizer Breast Cancer Research Fellowship will support my research in breast cancer, which focuses on targeting novel oncogenic pathways of cancer. My goal is to quickly translate new therapies to the bedside. This fellowship will also assist in my career development as I strive to be an independent investigator.
Scientific Statement of Research
Half of patients with triple-negative-breast-cancer (TNBC) do not respond to TNBC front-line therapy, and the disease eventually relapses with metastasis, leading to poor overall survival. Because TNBC exhibits higher levels of PD-L1 expression, tumor-infiltrating lymphocytes, and tumor mutant burden compared with other breast cancer subtypes, it likely responds better to immunotherapy. Numerous immunotherapy clinical trials for TNBC are ongoing and have demonstrated tremendous achievements. However, response rates are still far from satisfactory, as only about 10-20 percent of patients are responsive due to anti-PD-1/PD-L1 resistance and inadequate biomarkers for patient selection. Through non-biased methods, receptor tyrosine kinase Tyro3 has been identified as a major contributor to anti-PD-1/PD-L1 resistance. Results show Tyro3 could serve as a biomarker of anti-PD1/PD-L1 resistance and as a therapeutic target to overcome resistance.
Dr. Jiang is a postdoctoral fellow at the University of Texas MD Anderson Cancer Center. He received his PhD in December 2017 from Wuhan University, China, where he investigated the role of innate immunity in inflammatory diseases. In 2018, he joined Dr. Mien-Chie Hung’s lab at MD Anderson Cancer Center. His current research focus is the resistance mechanisms of anti-PD1/PD-L1 therapy and the identification of new biomarkers to predict resistance. He is also interested in studying new immunotherapy targets and looking for innovative therapeutic strategies by immune checkpoint antibodies and drugs conjugation.
Acknowledgement of Support
This fellowship will not only support my ongoing project but also promote my career development as a translational scientist in the cancer immunotherapy field. I sincerely appreciate Pfizer and the AACR for this fellowship opportunity. It is my great honor to receive this funding support.