Wanyi Chen, Postdoctoral Research Fellow at Dana-Farber Cancer Institute, shared a post on LinkedIn:
“I am happy to share that my Ph.D. thesis work is published in Cancer Discovery today!
In this study, we addressed a well-recognized yet not fully resolved challenge – the mechanism of resistance to antibody–drug conjugates (ADCs).
Using T-DXd as an example, we found that:
- loss of HER2 expression and
- mutations occurring at the T-DXd binding interface lead to reduced T-DXd internalization and ultimately decreased therapeutic efficacy.
As strategy to overcome resistance, we proposed combination treatment of T-DXd with Dato-DXd at low doses, which achieved similar or even better efficacy than a single high-dose ADC, with lower toxicity as well.
This work is the result of a wonderful collaboration between clinical fellows and research scientists, all driven by the shared goal of advancing cancer therapeutics and improving patients’ lives.
I would like to express my sincere gratitude to:
Sarat Chandarlapaty, my mentor, for his brilliant ideas, clear guidance, and continuous support throughout my Ph.D. and the publication process;
Avantika Gupta, PhD, for always being there to help overcome obstacles with warm support and encouragement;
Josh Drago, Nicholas Mai, and all clinical fellows, for their valuable input from the clinical side;
all our collaborators, for their significant contributions that made this work possible.
Looking ahead, we are eager to push this research toward clinical application and bring real benefits to patients in the near future!”
Title: Trastuzumab Deruxtecan (T-DXd) Resistance via Loss of HER2 Expression and Binding
Authors: Wanyi Chen, Avantika Gupta, Nicholas Mai, Sharanya Nag, Joshua S. Lau, Sukrit Singh, John D. Chodera, Bo Liu, Elisa de Stanchina, Fresia Pareja, Atif Ali Hashmi, Miriam M. Lieberman, Shanu Modi, Jacqueline Bromberg, Pedram Razavi, Joshua Z. Drago, Sarat Chandarlapaty
Read the Full Article.
