A new Houston Methodist-led study published in Clinical Cancer Research reports a breakthrough in understanding why some patients with metastatic breast cancer fail to respond to a common and important early-stage treatment.

Co-led by Stephen Wong, Ph.D., the John S Dunn Presidential Distinguished Chair in Biomedical Engineering and Professor of Radiology and Medicine at Houston Methodist, the study analysed 47 patients and 109 pretreatment metastatic lesions treated with trastuzumab deruxtecan (T-DXd).

The team identified S100–RAGE signalling—a pathway that functions as a communication system within cancer cells, helping them stay alive, grow, adapt to stress and resist treatment—as a key driver of early drug resistance in tumours.

As T-DXd becomes more common in early treatment of metastatic, understanding why some tumours fail to respond has become increasingly important.

“Our study suggested that S100–RAGE signalling may indicate early resistance to this drug and that even drug combination therapies may be less effective. But the exciting part is that this pathway appears targetable,” Wong said.

“Using therapeutic options to block the signalling pathway made the cancer cells sensitive to early-line treatment. In metastatic lab models, therapeutic combination with this early treatment significantly reduced metastatic lesion number, lesion size and overall tumour burden.”

According to the Centres for Disease Control and Prevention, breast cancer is the second most common cancer among women in the United States and the second leading cause of cancer death amongst women.

Data also shows that metastatic breast cancer has the lowest survival rate.

Other collaborators on the study are Hong Zhao (corresponding author), Wenjuan Dong Shiruo Wang, Bill Chan, Johnny Cui, James Sampson, Matthew Vazquez, Caitlin Sannes, Akshjot Puri and Jenny Chang from Houston Methodist; Wei Yang and Xiaoxian Li from Emory University.

The study was supported by grants from the National Institutes of Health, the John S. Dunn Research Foundation and the T.T. and W.F.Chao Foundation. To schedule an interview, contact Nathaniel Godwin, senior editor, research media relations at 681.285.8818 or nugodwin@houstonmethodist.org.

Source: Houston Methodist