A study co-led by researchers at UT Southwestern Medical Center and the University of Alabama at Birmingham suggests that combining EGFR inhibitors with standard chemotherapy could improve outcomes for glioblastoma, the most common primary brain cancer in adults. The findings were published in Science Translational Medicine.
Glioblastoma typically carries a poor prognosis, with most patients surviving only 12 to 18 months after diagnosis. Standard treatment usually involves surgery, radiation, and the chemotherapy drug temozolomide (TMZ). While TMZ damages cancer cell DNA to prevent division, tumors often develop resistance over time, leading to incurable recurrent disease. Current understanding indicates that TMZ works best in tumors lacking a specific DNA-repair protein called MGMT, but TMZ itself can increase MGMT production, complicating treatment.
The research team, including Dr. Amyn Habib of UT Southwestern and Dr. Gao Guo of UAB, investigated how the epidermal growth factor receptor (EGFR), a protein frequently mutated in glioblastoma, influences this process. Their work revealed that inhibiting EGFR significantly reduced the amount of MGMT produced by glioblastoma cells in laboratory settings. This effect was also observed in mouse models of the disease.
Further experiments tested whether an EGFR inhibitor named afatinib could make tumors more sensitive to TMZ, even in cases where resistance had already developed. The results showed that pretreating with afatinib one day before administering TMZ increased the cancer cells' sensitivity to the chemotherapy. However, administering both drugs simultaneously did not produce the same benefit. The researchers noted that MGMT production must be suppressed through EGFR inhibition before TMZ can effectively damage the DNA.
The study was co-led by Dr. Habib, a professor of neurology and neurological surgery at UT Southwestern, and Dr. Guo, an assistant professor of neurosurgery at UAB. Co-first authors included Arifa Nayab, a former member of the Habib Lab, and Nouman Mughal, a former assistant professor at Aga Khan University. Dr. Habib stated that the findings could offer new hope for the approximately 250,000 patients worldwide diagnosed with glioblastoma annually.
