Progress in phase III clinical trials of molecular targeted therapy and immunotherapy for glioblastoma

Abstract

Glioblastoma (GBM) is the most common primary central nervous system tumor, whose prognosis remains poor under the sequential standard of care, such as neurosurgery followed by concurrent temozolomide radiochemotherapy and adjuvant temozolomide chemotherapy in the presence or absence of tumor treating fields. Accordingly, the advent of molecular targeted therapy and immunotherapy has opened a new era of tumor management. A diverse range of targeted drugs have been tested in patients with GBM in phase III clinical trials. However, these drugs are ineffective for all patients, as evidenced by the fact that only a minority of patients in these trials showed prolonged survival. Furthermore, there are several published phase III clinical trials that involve immune checkpoint inhibitors, peptide vaccines, dendritic cell vaccines, and virotherapy. Accordingly, this review comprehensively overviews existing studies of targeted drugs and immunotherapy for glioma and discusses the challenge and perspective of targeted drugs and immunotherapy for glioma to clarify future directions.

Induction of ferroptosis by natural phenols: A promising strategy for cancer therapy

“…But the targets that through them ferroptosis is inhibited are different from those in cancer cells. In acute lung injury and Parkinson's disease, the main mechanism is attributed to the activation of NRF2 signaling (Deng et al, 2023;Lin et al, 2022), while in asthma and spinal cord injury, these effects are exerted through suppressing the immune response and, Id2/transferrin pathway, respectively (Wang, Li, Wang, Chen, & Goh, 2023;Wang, Li, Wang, Zhu, Liu, et al, 2023;Wang, Lin, Huang, Liu, Chen, et al, 2023;Wang, Liu, Li, Zha, Chen, et al, 2023;Wang, Shen, Lian, Deng, Qu, et al, 2023;Wang, Tan, Zhang, Wu, & Shi, 2023;Wang, Wan, Peng, Zhao, Bai, & Hu, 2023). This dual role, modulating NRF2 signaling, suppressing immune response, or affecting specific pathways, emphasizes the need for a nuanced understanding of quercetin's effects in different contexts.…”

“…Amentoflavone (AMF) is a natural biflavonoid compound isolated from plants such as ginkgo, hinoki, and St. John's wort (Tuli et al, 2023). Its anticancer features have been linked to its ability to induce cell cycle arrest, apoptosis, and autophagy alongside hindering metastasis and angiogenesis via modulating pathways such as the AMPK/mTOR pathway (Xiong et al, 2021), which is implicated in ferroptosis as well (Wang, Li, Wang, Chen, & Goh, 2023;Wang, Li, Wang, Zhu, Liu, et al, 2023;Wang, Lin, Huang, Liu, Chen, et al, 2023;Wang, Liu, Li, Zha, Chen, et al, 2023;Wang, Shen, Lian, Deng, Qu, et al, 2023;Wang, Tan, Zhang, Wu, & Shi, 2023;Wang, Wan, Peng, Zhao, Bai, & Hu, 2023). AMF has been shown to cause ferroptotic death in gastric cancer via downregulating a transcription factor named ATF2 and decreasing its target genes, including GPX4 and SLC7A11.…”

“…In osteoarthritis, curcumin safeguards chondrocytes from erastin-induced ferroptosis by upregulating the Nrf2 signaling pathway, which in turn reverses lipid ROS and Fe 2+ production (Zhou, Jia, et al, 2023). Additionally, curcumin's protective role extends to ligature-induced periodontitis, where it inhibits ferroptosis in periodontal-diseased mice by reducing MDA levels and modulating key ferroptosis-related proteins, including ACSL4, SLC7A11, GPX4, and TfR1 (Wang, Li, Wang, Chen, & Goh, 2023;Wang, Li, Wang, Zhu, Liu, et al, 2023;Wang, Lin, Huang, Liu, Chen, et al, 2023;Wang, Liu, Li, Zha, Chen, et al, 2023;Wang, Shen, Lian, Deng, Qu, et al, 2023;Wang, Tan, Zhang, Wu, & Shi, 2023;Wang, Wan, Peng, Zhao, Bai, & Hu, 2023). In hepatolenticular degeneration, curcumin's efficacy lies in its ability to expel copper and inhibit ferroptosis through the Nrf2/HO-1/GPX4 signaling pathway (Sun et al, 2023).…”

“…Preclinical investigations underscore curcumin's auspicious anti- Despite the imperative for subsequent clinical substantiation, curcumin, with its multifaceted biological activities, emerges as a compelling natural compound for cancer therapeutics (Wang, Li, Wang, Chen, & Goh, 2023;Wang, Li, Wang, Zhu, Liu, et al, 2023;Wang, Lin, Huang, Liu, Chen, et al, 2023;Wang, Liu, Li, Zha, Chen, et al, 2023;Wang, Shen, Lian, Deng, Qu, et al, 2023;Wang, Tan, Zhang, Wu, & Shi, 2023;Wang, Wan, Peng, Zhao, Bai, & Hu, 2023). Due to a wide range of studies regarding the role of curcumin in the induction of ferroptosis in cancer, we try to categorize the studies based on their targets.…”

“…Dong, et al, 2022;Han, Li, & Wu, 2022;Han, Lin, et al, 2022;Han, Yan, et al, 2022). ics, capsaicin demonstrates a potential therapeutic strategy in mitigating ferroptotic cell death in non-malignant conditions (Wang, Li, Wang, Chen, & Goh, 2023;Wang, Li, Wang, Zhu, Liu, et al, 2023;Wang, Lin, Huang, Liu, Chen, et al, 2023;Wang, Liu, Li, Zha, Chen, et al, 2023;Wang, Shen, Lian, Deng, Qu, et al, 2023;Wang, Tan, Zhang, Wu, & Shi, 2023;Wang, Wan, Peng, Zhao, Bai, & Hu, 2023).…”