Ding Fang Chuang1, Xuling Lin2. 1. Department of Neurology, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore, 308433, Singapore. 2. Department of Neurology, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore, 308433, Singapore. lin.xu.ling@singhealth.com.sg.
Abstract
PURPOSE OF REVIEW: Targeted therapies are part of biomarker-driven strategies that exploit actionable molecular targets and have gained traction following survival benefits demonstrated in various systemic malignancies. In glioblastoma, where therapeutic options remain scarce and prognosis poor, targeted therapies offer an attractive treatment alternative and are actively examined in clinical trials. In this review, we summarize the targeted therapies, including traditional small molecule inhibitors and monoclonal antibodies as well as immunotherapeutic approaches that are examined in clinical trials, and discuss the challenges of using them for the treatment of glioblastoma. RECENT FINDINGS: Despite initial speculations, phase II/III trials of targeted therapies in adult patients with glioblastoma have largely failed. Recent trials have focused on improving patient stratification, drug-tissue penetration, and target and compensatory pathway inhibition to optimize treatment response. In contrast to traditional small molecule and monoclonal antibody therapies, cancer immunotherapy may target specific molecular or immune checkpoint target(s) to trigger immune responses against glioblastoma. Early phase clinical trials of immunotherapy have shown encouraging results, and larger randomized trials are ongoing. Targeted therapies are being actively studied in clinical trials. Patients with glioblastoma should be prioritized for clinical trial participation.
PURPOSE OF REVIEW: Targeted therapies are part of biomarker-driven strategies that exploit actionable molecular targets and have gained traction following survival benefits demonstrated in various systemic malignancies. In glioblastoma, where therapeutic options remain scarce and prognosis poor, targeted therapies offer an attractive treatment alternative and are actively examined in clinical trials. In this review, we summarize the targeted therapies, including traditional small molecule inhibitors and monoclonal antibodies as well as immunotherapeutic approaches that are examined in clinical trials, and discuss the challenges of using them for the treatment of glioblastoma. RECENT FINDINGS: Despite initial speculations, phase II/III trials of targeted therapies in adult patients with glioblastoma have largely failed. Recent trials have focused on improving patient stratification, drug-tissue penetration, and target and compensatory pathway inhibition to optimize treatment response. In contrast to traditional small molecule and monoclonal antibody therapies, cancer immunotherapy may target specific molecular or immune checkpoint target(s) to trigger immune responses against glioblastoma. Early phase clinical trials of immunotherapy have shown encouraging results, and larger randomized trials are ongoing. Targeted therapies are being actively studied in clinical trials. Patients with glioblastoma should be prioritized for clinical trial participation.
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