2023 USMART Mentee: Hong Truong, MD, MS
By: Hong Truong, MD, MS, Penn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania | Posted on: 19 Sep 2023
I am a urologic oncology surgeon and a research investigator at Penn State Health Milton S. Hershey Medical Center. My goal is to become an independently funded surgeon-scientist with a strong focus on translational research in the field of cancer genomics. By investigating the inherited genetic variations, the somatic mutational landscape, and the interplay between germline and somatic alterations in cancer development, my aim is to methodically unravel the genetic underpinnings of urological cancers. This knowledge will directly translate into tangible benefits for patients, such as implementing high-risk screening protocols for early detection of cancer and developing innovative genotype-directed treatment strategies.
My current research focuses on the inherited genetics of patients with upper tract and bladder urothelial cancer. Urothelial cancer has a substantial hereditary component, with an estimated heritability of 30%,1 but the genetic mechanisms underlying familial aggregations and urothelial cancer development remain unknown. Recent large cohort studies demonstrated the likelihood of finding pathogenic germline variant in a cancer susceptibility gene in patients with urothelial cancer is high, ranging from 11% to 24% across the full spectrum of the disease.2-4 The causal effect of germline variant in DNA mismatch repair genes and the development of upper tract urothelial carcinoma is well known. Despite being a rare cancer, upper tract urothelial carcinoma is the third most common Lynch syndrome—associated cancer after colorectal and endometrial cancer.5 However, patients with upper tract urothelial carcinoma are infrequently referred for genetic evaluation. A hallmark of tumors in patients with Lynch syndrome is mismatch repair protein deficiency and microsatellite instability, which are important biomarkers of response to immunotherapy in various tumor types.6 Exploiting the therapeutic vulnerability of mismatch repair deficient/microsatellite unstable tumors in the management of upper tract urothelial carcinoma remains an untapped opportunity.
Over the next 3 to 5 years, my overarching goal is to build a comprehensive urological cancer genomics program at Penn State. This program will serve 2 critical purposes: (1) to decipher the genetic mechanisms of urothelial cancer and (2) to translate cutting-edge research into rational personalized care of patients with urological cancers. To achieve this, I plan to conduct pilot projects that provide genetic services including counseling, germline testing, and longitudinal follow-ups for patients who live outside of urban centers. Additionally, I aim to engage patient advocates and clinical stakeholders through focus groups to refine and improve research questions with the goal of incorporating genetic evaluation in the clinical care of patients with bladder and upper tract urothelial cancer.
The career path of a surgeon-scientist is both highly rewarding and persistently challenging. To excel in this field, I recognize the importance of maintaining surgical competency while pursuing cutting-edge research. I must learn to navigate patient care, secure research funding, lead a multidisciplinary research team, teach trainees, and balance ever-increasing administrative duties. I understand that I cannot embark on this journey alone. Just like an athlete, success cannot be achieved solely by understanding the process and emulating other surgeon-scientists. In order to thrive, I need the guidance of a coach and mentor who can impart the art and methodology of science and academia, helping me set realistic and attainable scientific and career goals.
Therefore, I consider myself incredibly fortunate to be a part of the AUA USMART (Urology Scientific Mentoring and Research Training) Academy. Through this program, I have been paired with Dr Ashish Kamat, an engaged and supportive mentor who possesses a wealth of knowledge and accomplishments as a physician-scientist. Dr Kamat has provided invaluable career support and guidance, assisting me in navigating the complexities of an academic career. Moreover, the USMART Academy fosters a vibrant community among early-career investigators through creative networking events. These occasions not only allow us to celebrate research achievements, but also provide a platform to share setbacks and challenges as we embark on our respective academic journeys.
- Mucci LA, Hjelmborg JB, Harris JR, et al. Familial risk and heritability of cancer among twins in Nordic countries. JAMA. 2016;315(1):68-76.
- Carlo MI, Ravichandran V, Srinavasan P, et al. Cancer susceptibility mutations in patients with urothelial malignancies. J Clin Oncol. 2020;38(5):406-414.
- Nassar AH, Abou Alaiwi S, AlDubayan SH, et al. Prevalence of pathogenic germline cancer risk variants in high-risk urothelial carcinoma. Genet Med. 2020;22(4):709-718.
- Pietzak EJ, Whiting K, Srinivasan P, et al. Inherited germline cancer susceptibility gene variants in individuals with non-muscle-invasive bladder cancer. Clin Cancer Res. 2022;28(19):4267-4277.
- Koornstra JJ, Mourits MJ, Sijmons RH, Leliveld AM, Hollema H, Kleibeuker JH. Management of extracolonic tumours in patients with Lynch syndrome. Lancet Oncol. 2009;10(4):400-408.
- Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357(6349):409-413.