Computer Simulations Predict Treatment for HER2-Mutated Breast Cancer

Ron Bose, MD, PhD, discusses the importance of computer simulations to develop treatments for patients with HER2-positive breast cancer as established by a recent study.

Ron Bose, MD, PhD, associate professor in the department of medicine at the Washington University School of Medicine in St. Louis, discusses the importance of computer simulations to develop treatments for patients with HER2-positive breast cancer.

Bose highlights the methods and results of a recent study by Ariella B. Hanker, PhD, et al, which explored solutions to drug resistance against various approved treatments for HER2-positive breast cancer.

According to Bose, computer simulation of protein function played a crucial role in identifying molecular-targeted therapies related to HER2 mutations. Using these simulations of protein structure, Hanker and fellow investigators were able to predict that co-occurring mutations in HER2 and HER3 genes would enhance PI3K-AKT activation, identifying a potential combination of neratinib (Nerlynx) and a PI3K alpha inhibitor, alpelisib (Piqray) to inhibit the growth of cancer cells.

Protein structure simulations can quickly determine whether mutations will play a role in drug resistance, helping oncologists predict the outcomes of existing and new treatments, Bose says. With the rising usage of next-generation sequencing (NGS) in identifying mutations that are biomarkers or oncogenic drivers, increasingly detailed simulations of protein interactions identify areas of investigation for new treatments and provide more options for targeted therapies.


0:08 | One thing that I found novel for the study was their use of computer-based simulations for how these mutations affect protein structure and function. As we're getting into the evaluation, and trying to figure out how to target more and more cancer mutations identified by NGS, these computer simulations are very powerful because they can rapidly assess, "What is the consequence of these mutations? Are these mutations functionally silent? Or are these mutations potentially functionally important? And what impact do they have on protein function overall?" So, these computer simulations are a very important direction, and as with so many things that are computer-based, the field of computer simulations of protein structure and functions is really racing ahead, and it's something that oncologists might want to have some appreciation for, because I think we will see it more and more in future studies.

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