Diagnostic and therapeutic avenues for glioblastoma: no longer a dead end?

Abstract

Glioblastomas are heterogeneous neoplasms that are driven by complex signalling pathways, and are among the most aggressive and challenging cancers to treat. Despite standard treatment with resection, radiation and chemotherapy, the prognosis of patients with glioblastomas remains poor. An increasing understanding of the molecular pathogenesis of glioblastomas has stimulated the development of novel therapies, including the use of molecular-targeted agents. Identification and validation of diagnostic, prognostic and predictive biomarkers has led to the advancement of clinical trial design, and identification of glioblastoma subgroups with a more-favourable prognosis and response to therapy. In this Review, we discuss common molecular alterations relevant to the biology of glioblastomas, targeted, antiangiogenic and immunotherapies that have impacted on the treatment of this disease, and the challenges and pitfalls associated with these therapies. In addition, we emphasize current biomarkers relevant to the management of patients with glioblastoma.

Advances in Diagnostic and Treatment Modalities for Intracranial Tumors

“…Despite these classifications, optimal targeted treatment still may require individualized characterization of specific markers in individual tumors (Fig 4). 103, 104, 105, 106 …”

“…A majority of targeted therapies involve either antibodies or small molecule inhibitors, and many have been investigated in human brain tumors with minimal activity demonstrated to date 104. This may be a reflection of many factors including insufficient characterization of both tumors and patients, as well as the potential need for multiple target strategies.…”

A CREB1–TGFβ2 Self-Sustaining Loop in Glioblastoma

“…Grade 4 glioma, or glioblastoma (GBM), is the most aggressive and shows minimal response to current therapies ( 1 ). Standardof-care therapies include surgical resection and a combination of radiotherapy and chemotherapy, but tumor recurrence is rapid, and the median survival following treatment remains signifi cantly below 2 years.…”

Accessibilome of Human Glioblastoma: Collagen-VI-alpha-1 Is a New Target and a Marker of Poor Outcome

“…14 Briefly, fresh tissue samples (of human and CAM origin) were first cut in smaller pieces (∼0.125 cm 3 ) and immediately soaked into EZ-link Sulfo NHS-SS-biotin (Pierce, Rockford, IL) solution for 15 min, then snap-frozen and pulverized. 1 mg of tissue powder was lysed and subjected to affinity purification of biotinylated proteins using streptavidin.…”

“…These consist of small molecules or antibodies, both directed against aberrantly amplified growth factor receptors (and resulting pathways) found on tumor cells (e.g., PDGFR and EGFR) or in tumor-associated vasculature (VEGFR). 3,4 Although the progress made is stunning, 5 the benefits to the patient remain modest despite the enormous financial cost. 6 Biodistribution studies based on PET (positron emission tomography) imaging show that small molecules do not selectively accumulate in tumors, 7 requiring high, often toxic doses for achieving therapeutic effects.…”