A phase II trial with cetuximab, bevacizumab, and irinotecan for patients with primary glioblastomas and progression after radiation therapy and temozolamide

Lassen, U.; Hasselbalch, Benedikte; Sørensen, M.; Holmberg, M.; Hansen, S.; Kosteljanetz, Michael; Laursen, Henning; Poulsen, Hans Skovgaard

doi:10.1200/jco.2008.26.15_suppl.2056

Cited by 4 publications

(1 citation statement)

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“…In a phase II study,40 cetuximab as a single agent was safe and well tolerated in patients with recurrent high‐grade glioma; PFS‐6 and overall survival (OS) rates were 10% and 40%, respectively. In a phase II study,41 cetuximab, bevacizumab, and irinotecan therapy was evaluated in recurrent GBM. One complete response (CR) and 8 PRs were observed (response rate [RR], 33%), and 5 patients (19%) had minor responses (MRs), of 32 patients.…”

Section: Molecularly Targeted Therapies For Gliomamentioning

confidence: 99%

Molecularly targeted therapies for glioma

Yamanaka

Saya

2009

Annals of Neurology

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Over the past decade, molecularly targeted therapies have been added to cytotoxic and antiendocrine drugs in the treatment of cancer, with the aim of targeting the molecular pathways that underlie the carcinogenic process and maintain the cancer phenotype. Success with some of these agents has suggested that identification and validation of drug targets is the starting point for the development of active, safe, and effective drugs. The main molecular targets used to develop anticancer drugs are cell surface receptors, signal transduction pathways, gene transcription targets, ubiquitin-proteasome/heat shock proteins, and tumor microenvironment components. Here, we review the development of the main molecularly targeted noncytotoxic agents studied in glioma, highlighting lessons derived from the development of these novel drugs and proposing new horizons for the clinical development of molecularly targeted therapies.

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Section: Molecularly Targeted Therapies For Gliomamentioning

confidence: 99%

Molecularly targeted therapies for glioma

Yamanaka

Saya

2009

Annals of Neurology

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EGFR^vIII: An Oncogene with Ambiguous Role

Rutkowska

Stoczyńska-Fidelus

Janik

et al. 2019

Journal of Oncology

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Epidermal growth factor receptor variant III (EGFRvIII) seems to constitute the perfect therapeutic target for glioblastoma (GB), as it is specifically present on up to 28–30% of GB cells. In case of other tumor types, expression and possible role of this oncogene still remain controversial. In spite of EGFRvIII mechanism of action being crucial for the design of small active anticancer molecules and immunotherapies, i.e., CAR-T technology, it is yet to be precisely defined. EGFRvIII is known to be resistant to degradation, but it is still unclear whether it heterodimerizes with EGF-activated wild-type EGFR (EGFRWT) or homodimerizes (including covalent homodimerization). Constitutive kinase activity of this mutated receptor is relatively low, and some researchers even claim that a nuclear, but not a membrane function, is crucial for its activity. Based on the analyses of recurrent tumors that are often lacking EGFRvIII expression despite its initial presence in corresponding primary foci, this oncogene is suggested to play a marginal role during later stages of carcinogenesis, while even in primary tumors EGFRvIII expression is detected only in a small percentage of tumor cells, undermining the rationality of EGFRvIII-targeting therapies. On the other hand, EGFRvIII-positive cells are resistant to apoptosis, more invasive, and characterized with enhanced proliferation rate. Moreover, expression of this oncogenic receptor was also postulated to be a marker of cancer stem cells. Opinions regarding the role that EGFRvIII plays in tumorigenesis and for tumor aggressiveness are clearly contradictory and, therefore, it is crucial not only to determine its mechanism of action, but also to unambiguously define its role at early and advanced cancer stages.

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