VCU Massey and MD Anderson Researchers Launch $7.3M Clinical Trial Targeting Cancer Stem Cells in Metastatic Triple-Negative Breast Cancer
核心洞察
A multidisciplinary team at VCU Massey Comprehensive Cancer Center (搜索) and MD Anderson Cancer Center received a $7.3 million U.S. Department of Defense grant to fund a novel clinical trial for metastatic triple-negative breast cancer (搜索).
The trial will test the combination of naxitamab, targeting the newly identified GD2 (搜索) marker on cancer stem cells, with FDA-approved sacituzumab govitecan to overcome treatment resistance.
GD2 (搜索) is overexpressed in more than half of TNBC (搜索) tumors and is found on cancer stem cells that contribute to cell proliferation, metastasis, and worse patient outcomes.
A multidisciplinary team of researchers at VCU Massey Comprehensive Cancer Center (搜索) and MD Anderson Cancer Center has been awarded a $7.3 million grant from the U.S. Department of Defense to fund a novel clinical trial targeting one of the most aggressive and hard-to-treat forms of breast cancer (搜索): metastatic triple-negative breast cancer (搜索) (TNBC (搜索)). The study marks a significant step toward transforming treatment regimens and improving outcomes for patients with metastatic TNBC.
Targeting Cancer Stem Cells Through GD2 Marker
The clinical trial (NCT07011654) is based on groundbreaking preclinical research led by Vekata Lokesh Battula, Ph.D., who recently joined Massey as its assistant director of Cancer Research Training and Education Coordination (CRTEC) Efforts and professor in the Department of Internal Medicine at the VCU School of Medicine. Battula's work at MD Anderson helped identify a new marker in patients with TNBC (搜索) called GD2 (搜索), which is expressed on cancer stem cells that contribute to cell proliferation and metastasis and correlate with worse patient outcomes.
"We have found that GD2 (搜索), a surface marker, is overexpressed in more than half of TNBC (搜索) tumors. Our data indicate that GD2-expressing TNBC cells could be targeted using anti-GD2 monoclonal antibodies," Battula said. "Our studies have identified a novel therapeutic strategy to identify and eliminate these treatment-resistant cancer stem cells."
Combination Therapy Approach
The trial will test the safety and efficacy of combining two therapies – naxitamab, a targeted antibody therapy directed against GD2 (搜索), and sacituzumab govitecan, an FDA-approved chemotherapy-based treatment used in metastatic TNBC (搜索). If successful, this study will be the first to overcome TNBC's resistance to sacituzumab govitecan by eliminating breast cancer (搜索) stem cells, potentially paving the way for more durable responses in patients with metastatic TNBC.
"In targeting GD2 (搜索) with naxitamab, we are hoping to eradicate the root cause of resistance and boost the long-term effectiveness of sacituzumab govitecan," Battula explained. "I look forward to successful outcomes from this trial, especially because we try to eliminate the cells that are the root cause of the origin of cancer and its spread in patients with TNBC (搜索)."
Clinical Trial Structure and Collaboration
MD Anderson will open and enroll patients in the clinical trial, with research specimens collected from enrolled patients sent to Battula for analysis to be conducted at VCU. The trial is led by Clinton Yam, M.D., associate professor of Breast Medical Oncology at MD Anderson, along with Battula. This project also benefits from strategic collaborations with the University of Hawai'i Cancer Center (搜索) and the Houston Methodist Research Institute.
Addressing Treatment Resistance in TNBC
TNBC (搜索) is an aggressive and heterogeneous type of breast cancer (搜索) with few therapeutic options due to being resistant to anti-hormone and anti-HER2 therapies, lacking targeted treatment options once it has spread beyond the breast and nearby lymph nodes. One major reason for treatment failure is the persistence of breast cancer stem cells, a rare population of tumor-initiating cells that can survive standard therapies by entering a dormant state. These cells can later re-emerge and drive tumor recurrence.