A nationwide study aimed at finding better treatments for the aggressive metaplastic breast cancer has discovered two promising inhibitor medications that could hinder the progression of the disease.
A nationwide study aimed at finding better treatments for the aggressive metaplastic breast cancer has discovered two promising inhibitor medications that could hinder the progression of the disease.
The research team from Houston Methodist and various institutions across the country investigated the biology of metaplastic breast cancer, contrasting it with non-metaplastic triple-negative breast cancer. They found that metaplastic breast cancers usually have two distinct signaling pathways involved in cell communication. The researchers managed to interrupt these pathways using a class of inhibitors known as phosphoinositide 3-kinase inhibitors (P13K), typically employed for advanced cancers, combined with nitric oxide inhibitors (NOS), which treat septic shock, cardiovascular issues, and other ailments. When these drugs were applied to the cells, they effectively disrupted the pathways, enhancing treatment efficacy.
Metaplastic breast cancer is a rare and aggressive type that generally grows more rapidly and is more likely to spread to other regions of the body compared to other breast cancer types. This variant also has a higher chance of recurring after initial treatments. Most patients suffering from metaplastic breast cancer often receive the same treatment as those with triple-negative breast cancer, another aggressive variant, but metaplastic breast cancer frequently shows poor response.
The results of this study are detailed in the article titled, “NOS inhibition sensitizes metaplastic breast cancer to PI3K inhibition and taxane therapy via c-JUN repression,” published in Nature Communications, which is part of the Nature group of journals. Dr. Jenny Chang, who is the executive vice president, president and CEO, as well as the chief academic officer at the Houston Methodist Academic Institute, is the corresponding author. Dr. Chang holds the Ernest Cockrell, Jr. Presidential Distinguished Chair at the institute and previously directed the Dr. Mary and Ron Neal Cancer Center at Houston Methodist.
“This significant discovery presents a hopeful treatment alternative for one of the most aggressive and challenging subtypes of breast cancer,” Dr. Chang stated. “We have the opportunity to enhance outcomes for patients who currently have limited treatment options and poor prognoses, representing a meaningful advancement in cancer research and treatment.”
The lead author, Dr. Tejaswini Reddy, is optimistic that this research will contribute to creating specific care plans for those with metaplastic breast cancer and enhance long-term survival rates.
“Our research showcases a promising combination of therapies that could potentially transform the treatment landscape for metaplastic breast cancer. It is essential to transform these findings into a clinical trial funded by the National Cancer Institute to improve outcomes for patients facing this rare and aggressive disease. Additionally, this approach may extend benefits to patients with other cancers that share similar biological traits,” Dr. Reddy explained.
The insights from this preclinical research have already paved the way for a National Cancer Institute (NCI)-funded Phase 2 clinical trial aimed at assisting patients with this rare and aggressive form of cancer (https://clinicaltrials.gov/study/NCT05660083).
Collaborators on this study alongside Dr. Chang include: Tejaswini Reddy, Akshjot Puri, Liliana Guzman-Rojas, Christoforos Thomas, Wei Qian, Jianying Zhou, Hong Zhao, Bijan Majboubi, Andrian Oo, Young-Jae Cho, Baek Kim, Jose Thaiparambil, Roberto Rosato, Karina Ortega Martinez, Maria Florencia Chevaro, Camila Ayerbe, Noah Giese, David Wink, Stephen Lockett, Stephen Wong, Jeffrey Chang, Savitri Krishnamurthy, Clinton Yam, Stacy Moulder, Hele Piwnica-Worms, and Funda Meric-Bernstam.
This research received support from NCI grants, the Breast Cancer Research Foundation, CREDO, NIAID, as well as charitable contributions from Dr. Mary & Ron Neal.
