Glioblastoma is a highly aggressive and challenging form of brain cancer. Selinexor, an investigational drug, is currently being explored as a potential therapeutic approach for glioblastoma. This ongoing research aims to understand its efficacy and safety profile, offering a new avenue in the complex landscape of brain cancer treatment.
Understanding Glioblastoma
Glioblastoma (GBM) stands as the most common and aggressive primary brain tumor in adults, characterized by its rapid growth and diffuse infiltration into healthy brain tissue. Its invasive growth pattern often prevents complete surgical removal, leaving behind microscopic tumor cells.
Standard treatment approaches typically involve a combination of maximal surgical resection, followed by radiation therapy and chemotherapy, often using temozolomide. Despite these efforts, glioblastoma remains largely incurable due to factors like its ability to bypass the blood-brain barrier and develop resistance to conventional therapies. The median overall survival for patients with glioblastoma remains low.
How Selinexor Works Against Glioblastoma
Selinexor is a selective inhibitor of nuclear export (SINE) compound. This oral medication targets and blocks Exportin 1 (XPO1), a protein overexpressed in many cancers, including glioblastoma. XPO1’s normal function involves transporting various proteins, including tumor suppressor proteins, from the cell nucleus to the cytoplasm.
By inhibiting XPO1, selinexor causes tumor suppressor proteins, such as p53, p21, and p27, to accumulate within the cell nucleus. This nuclear retention allows them to reactivate their tumor-suppressing functions, which can lead to cell cycle arrest and apoptosis. Selinexor also hinders the export of messenger RNAs (mRNAs) that promote cancer cell growth and survival. This multifaceted mechanism disrupts cellular processes that glioblastoma cells rely on for their uncontrolled proliferation.
Clinical Research and Outcomes
Clinical trials have investigated selinexor’s effects in glioblastoma patients, including an international phase 2 study. This study evaluated different dosing schedules and assessed the drug’s safety and effectiveness. Researchers observed that selinexor could penetrate brain tumors, reaching measurable concentrations.
The phase 2 study explored different selinexor doses and schedules. For instance, in one arm, a weekly 80 mg dose of selinexor showed a 6-month progression-free survival rate (PFS6) of 17%, with a measurable reduction in tumor size observed in 28% of patients across the medical arms. The overall response rate, including partial or complete responses, was 8.8% across the medical arms, with one complete and two durable partial responses noted in the 80 mg once-weekly arm. Common side effects reported in these trials included fatigue (61%), nausea (59%), decreased appetite (43%), and low platelet counts (thrombocytopenia, 43%). These side effects were manageable through supportive care and dose adjustments.
Current Treatment Landscape and Outlook
Selinexor is an investigational drug for glioblastoma and is not approved for its treatment. However, it has received FDA approval for other cancer types, such as refractory multiple myeloma and relapsed/refractory diffuse large B-cell lymphoma. Its potential role in glioblastoma is being explored for recurrent glioblastoma, where treatment options are limited.
Research continues to investigate selinexor, sometimes in combination with other therapies like radiation or temozolomide, for both newly diagnosed and recurrent glioblastoma. Preclinical studies have indicated that selinexor may act synergistically when combined with these standard treatments. While selinexor shows promise as a new therapeutic avenue, it is still under investigation and not a definitive cure. The complex nature of glioblastoma necessitates continued research to develop more effective and durable treatment strategies.