Investigating PINCH-1 in Glioblastoma Multiforme: A Potential Adjuvant Therapy Target to Improve Treatment Outcomes

Gliomas account for approximately 80% of all brain cancers and 30% of central nervous system tumors. Glioblastoma multiforme (GBM), the most common, is unfortunately, the most aggressive glioma cancer type. Despite treatment efforts such as surgery, radiation, and chemotherapy, nearly all low-grade astrocytoma progress to GBM without complete surgical resection. Achieving full surgical removal is typically impossible, leading to an almost 100% recurrence rate of GBM after 9 months with a median survival of approximately 15 months. This poor prognosis is due to its high invasiveness and resistance to therapy. Therefore, improved therapeutic approaches are needed to reduce recurrence and prevent progression of astrocytoma into GBM. This research investigated how the particularly interesting new cysteine-histidine-rich protein 1 (PINCH-1) protein may lead to a potential adjuvant therapy to supplement surgery, radiation, and chemotherapy. The PINCH protein is highly expressed during development for cytoskeletal organization, cell migration, extracellular matrix and focal adhesion interactions, as well as, cell survival. However, after birth, PINCH-1 is nearly undetectable in healthy cells, but resurges in cancer cells. Though PINCH-1 has been linked to various cancers by several studies, little is known about the mechanistic and signaling pathways whereby PINCH contributes to the development and recurrence of GBM and resistance of cancer cells to therapeutic intervention. Our study investigated the consequences of changes in PINCH-1 protein expression, cell cycle alterations, post-translational modifications, and cell survival in GBM cell sensitivity to chemotherapeutic agents. Further studies are required to identify potential pathways to modify PINCH1 for use as an adjuvant therapy to accompany surgical, chemotherapeutic, and radiation treatment.