A New Study Reveals How Mutations in the HER3 Gene Can Impact Cancer Treatments For Mutations in the HER2 Gene

            

Hanker, Ariella, and Dan Ye. “‘Normal Breast Epithelial Cells Were Engineered to Express Mutant HER3 Alone, Mutant HER2 Alone, or Both Mutations. Cells Expressing Only the HER3 Mutation Formed Very Small Spherical Colonies in a 3D Matrix, Which Mimics the Tumor Microenvironment. Cells Expressing Only the HER2 Mutation Formed Large Spherical Colonies with Smooth Edges. However, Cells Expressing Both Mutations Formed Large Colonies with Invasive Branches, Indicating Cells Invading into the Extracellular Matrix.".” UT Southwestern Medical Center, UT Southwestern Medical Center, 24 June 2021, www.utsouthwestern.edu/newsroom/articles/year-2021/her3-gene-mutations.html. 

        A new study has found that mutations in the gene HER3, a gene related to the gene HER2, a gene often involved in breast cancers and other malignant tumors,  can increase activity that causes tumor growth. This study investigated how HER3 and HER2 interact in response to cancer treatment targeting the mutated version of HER2. The study leader, Ariella B. Hanker, Ph.D., stated that commonly only one mutant gene is targetted with a treatment drug. Still, this study demonstrated how other mutant genes must be examined with certain cancer patients. In clinical studies, it has been found that utilizing medicines that inhibit the mutant form of the HER2 gene’s functions can lead to tumor shrinkage. Certain patients, however, do not respond to these treatments, and their tumors did not shrink. Dr. Hanker, along with the study’s co-leader, Carlos L. Arteaga, M.D, looked into how the mutant forms of the HER2 and the HER3 proteins react to each other.  The study team first used a computer model, which displayed the proteins of the mutant forms of the HER2 and the HER3 genes binding together in a much stronger manner compared to the nonmutant forms of gene proteins.

 This prediction appeared correct in the lab when the study team combined the HER2 and the HER3 mutant proteins. Another computer model displayed that the HER2 and the HER3 proteins binding prevented inhibitor drugs targeting the HER2 proteins from binding together, thus rendering the drug ineffective. In response to these findings, Dr. Hanker has stated, “Patients that carry both HER2 and HER3 mutations are likely not going to be good candidates for treatments by HER2 inhibitors themselves,”. More so, Dr. Hanker also states, “By also inhibiting the action of HER3, we can make some headway against these tumors.”. This remarkable study has shown how to treat forms of breast cancer caused by mutations in the HER2 and HER3 genes more effectively. By using drugs that also inhibit the function of the HER3 gene, doctors will be able to treat more cancer patients effectively. Hopefully, more will be able to overcome the disease with this newfound knowledge. 

Link to the article: https://www.utsouthwestern.edu/newsroom/articles/year-2021/her3-gene-mutations.html

Link to the study: https://www.cell.com/cancer-cell/pdf/S1535-6108(21)00284-1.pdf