Role of glioblastoma stem cells in cancer therapeutic resistance: a perspective on antineoplastic agents from natural sources and chemical derivatives

Autor(es)

Alves, Ana Laura V. ^[1] ; Gomes, Izabela N. F. ^[1] ; Carloni, Adriana C. ^[1] ; Rosa, Marcela N. ^[1] ; da Silva, Luciane S. ^[1] ; Evangelista, Adriane F. ^[1] ; Reis, Rui Manuel ^{[1, 2, 3]} ; Silva, Viviane Aline O. ^[1]

Afiliação do(s) autor(es)

^[1] Barretos Canc Hosp, Mol Oncol Res Ctr, Rua Antenor Duarte Villela 1331, BR-14784400 Barretos, SP - Brazil

^[2] ICVS 3Bs PT Govt Associate Lab, P-4806909 Braga - Portugal

^[3] Univ Minho, Life & Hlth Sci Res Inst ICVS, Sch Med, P-4710057 Braga - Portugal

• Tipo de documento: Artigo de Revisão
• Fonte: STEM CELL RESEARCH & THERAPY; v. 12, n. 1 MAR 24 2021.
• Citações Web of Science: 0

Resumo

Glioblastoma (GBM) is the highest-grade form of glioma, as well as one of the most aggressive types of cancer, exhibiting rapid cellular growth and highly invasive behavior. Despite significant advances in diagnosis and therapy in recent decades, the outcomes for high-grade gliomas (WHO grades III-IV) remain unfavorable, with a median overall survival time of 15-18months. The concept of cancer stem cells (CSCs) has emerged and provided new insight into GBM resistance and management. CSCs can self-renew and initiate tumor growth and are also responsible for tumor cell heterogeneity and the induction of systemic immunosuppression. The idea that GBM resistance could be dependent on innate differences in the sensitivity of clonogenic glial stem cells (GSCs) to chemotherapeutic drugs/radiation prompted the scientific community to rethink the understanding of GBM growth and therapies directed at eliminating these cells or modulating their stemness. This review aims to describe major intrinsic and extrinsic mechanisms that mediate chemoradioresistant GSCs and therapies based on antineoplastic agents from natural sources, derivatives, and synthetics used alone or in synergistic combination with conventional treatment. We will also address ongoing clinical trials focused on these promising targets. Although the development of effective therapy for GBM remains a major challenge in molecular oncology, GSC knowledge can offer new directions for a promising future. (AU)

• Processo FAPESP: 17/22305-9 - Estudo de biomarcadores de resposta ao cetuximabe e perspectivas do uso de combi-moléculas anti-EGFR em tumores sólidos
• Beneficiário: Izabela Natalia Faria Gomes
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 19/05142-4 - Caracterização do efeito biológico do composto semissintético derivado de Euphorbia tirucalli in vitro e in vivo, a partir do estabelecimento de um modelo xenográfico derivado de pacientes com tumores no trato gastrointestinal
• Beneficiário: Ana Laura Vieira Alves
• Modalidade de apoio: Bolsas no Brasil - Doutorado