Glioblastoma stem-like cells: at the root of tumor recurrence and a therapeutic target

Abstract

Glioblastoma is the most common and most aggressive primary brain malignancy. The current initial standard of care consists of maximal safe surgical resection followed by radical radiotherapy and adjuvant temozolomide. Despite optimal therapy, median survival is ~15 months from diagnosis in molecularly unselected patients, and <6 months for patients with recurrent disease. Therefore, clinical treatments are currently palliative, not curative. Collectively, current knowledge suggests that the continued tumor growth and recurrence is in part due to the presence of glioma stem-like cells, which display self-renewal and tumorigenic potential. They differ from their more differentiated progeny, as they are more resistant to current treatments. Recurrent disease may be a consequence of the enhancement and/or gain of stem cell-like characteristics during disease progression, together with preferential death of more differentiated tumor cells during treatment, signifying that the cancer stem cell phenotype is a crucial therapeutic target. The limited knowledge of the characteristics of these cells and their response to current clinical treatments warrants intensive investigation with the aim to improve patient survival and/or develop a cure for this disease.

Magnetic hyperthermia therapy for the treatment of glioblastoma: a review of the therapy’s history, efficacy and application in humans

“…The standard of care for patients with GBM begins with maximal surgical resection, when possible, and continues with a combination of radiation therapy (RT) and chemotherapy followed by chemotherapy alone [5]. The tumour almost always recurs locally due to infiltrating cancer cells which reside away from the tumour bulk [6,7]. These cells are located beyond the contrast enhancing tumour visualised on magnetic resonance imaging (MRI) and are difficult to resect since they reside among healthy cells.…”

Assessment of Anti-Proliferative Activities of Selected Medicinal Plant Extracts Used for Management of Diseases around Lake Victoria Basin

“…The current paradigm of gliomagenesis revolves around GSCs, which have been recognized as the most clinically relevant type of glioma cells that are primarily responsible for the maintenance of tumour growth [51]. Owing to their unique biological properties such as unlimited self-renewal propensity, infinite proliferative capacity, phenotypic and functional plasticity, and superior ability to survive cytotoxic insults that are lethal for non-stem gioma cells, GSCs have emerged as a key factor in therapy resistance and, consequently, a prime candidate for therapeutic targeting in GBs [52][53][54][55][56]. Delineating the molecular mechanisms underlying the GSCs ability to survive cytotoxic treatments and drive post-treatment growth of malignant gliomas has been recognized as the matter of prime importance to improve current therapeutic strategies.…”

Gambogic Acid Efficiently Kills Stem-Like Colorectal Cancer Cells by Upregulating ZFP36 Expression

“…CSCs are therefore considered to be the primary cause of tumor treatment failure, due to their resistance to conventional therapies [12-14]. Therefore, inhibiting the growth of tumoral CSCs is critically important for cancer treatment.…”