Highlighted Advances in Therapies for Difficult-To-Treat Brain Tumours Such as Glioblastoma

Cruz, Nuno; Herculano-Carvalho, Manuel; Roque, Diogo; Faria, Cláudia; Cascão, Rita; Ferreira, Hugo Alexandre; Reis, Catarina Pinto; Matela, Nuno

doi:10.3390/pharmaceutics15030928

Cited by 7 publications

(7 citation statements)

References 166 publications

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“…Despite the advances associated with the incorporation of TTFields to GB treatment, its clinical use is still quite restricted. EANO guidelines argue that the clinical benefit of TTFields has not been established yet, which contradicts the ASCO-NSO recommendations [ 253 , 347 ]. Certainly, price, regulation, the increase in the efficacy of combined treatments, and likely the development of novel intracranial electrodes, may assist in increasing the utilization and acceptance of TTFields [ 316 ].…”

Section: Present Therapy and Challengesmentioning

confidence: 99%

Glioblastoma Therapy: Past, Present and Future

Obrador,

Moreno-Murciano,

Oriol-Caballo

et al. 2024

IJMS

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Glioblastoma (GB) stands out as the most prevalent and lethal form of brain cancer. Although great efforts have been made by clinicians and researchers, no significant improvement in survival has been achieved since the Stupp protocol became the standard of care (SOC) in 2005. Despite multimodality treatments, recurrence is almost universal with survival rates under 2 years after diagnosis. Here, we discuss the recent progress in our understanding of GB pathophysiology, in particular, the importance of glioma stem cells (GSCs), the tumor microenvironment conditions, and epigenetic mechanisms involved in GB growth, aggressiveness and recurrence. The discussion on therapeutic strategies first covers the SOC treatment and targeted therapies that have been shown to interfere with different signaling pathways (pRB/CDK4/RB1/P16ink4, TP53/MDM2/P14arf, PI3k/Akt-PTEN, RAS/RAF/MEK, PARP) involved in GB tumorigenesis, pathophysiology, and treatment resistance acquisition. Below, we analyze several immunotherapeutic approaches (i.e., checkpoint inhibitors, vaccines, CAR-modified NK or T cells, oncolytic virotherapy) that have been used in an attempt to enhance the immune response against GB, and thereby avoid recidivism or increase survival of GB patients. Finally, we present treatment attempts made using nanotherapies (nanometric structures having active anti-GB agents such as antibodies, chemotherapeutic/anti-angiogenic drugs or sensitizers, radionuclides, and molecules that target GB cellular receptors or open the blood–brain barrier) and non-ionizing energies (laser interstitial thermal therapy, high/low intensity focused ultrasounds, photodynamic/sonodynamic therapies and electroporation). The aim of this review is to discuss the advances and limitations of the current therapies and to present novel approaches that are under development or following clinical trials.

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Section: Present Therapy and Challengesmentioning

confidence: 99%

Glioblastoma Therapy: Past, Present and Future

Obrador,

Moreno-Murciano,

Oriol-Caballo

et al. 2024

IJMS

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“…Advanced radiotherapy techniques, such as intensity-modulated radiation therapy and stereotactic radiosurgery, have been developed to improve the outcomes of radiotherapy in GBM. [75,76] IMRT allows for the delivery of higher radiation doses to the tumor while sparing normal tissues, thereby reducing the risk of radiation-related toxicity. [77] SRS involves the delivery of a high dose of radiation to the tumor in a single fraction, using a highly precise targeting system.…”

Section: Conventional Treatments For Glioblastomamentioning

confidence: 99%

“…[79] Chemotherapy drugs work by targeting rapidly dividing cancer cells and preventing them from growing and dividing. [75] The most commonly used include temozolomide (TMZ) and carmustine (BCNU). [80] Newer chemotherapy drugs, for example, bevacizumab and temsirolimus, have been investigated in clinical trials for the GBM management.…”

Section: Conventional Treatments For Glioblastomamentioning

confidence: 99%

Targeting inflammation in glioblastoma: An updated review from pathophysiology to novel therapeutic approaches

Alorfi,

Ashour,

Alharbi

et al. 2024

Medicine

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Glioblastoma (GBM) is a highly aggressive primary malignant brain tumor with a dismal prognosis despite current treatment strategies. Inflammation plays an essential role in GBM pathophysiology, contributing to tumor growth, invasion, immunosuppression, and angiogenesis. As a result, pharmacological intervention with anti-inflammatory drugs has been used as a potential approach for the management of GBM. To provide an overview of the current understanding of GBM pathophysiology, potential therapeutic applications of anti-inflammatory drugs in GBM, conventional treatments of glioblastoma and emerging therapeutic approaches currently under investigation. A narrative review was carried out, scanning publications from 2000 to 2023 on PubMed and Google Scholar. The search was not guided by a set research question or a specific search method but rather focused on the area of interest. Conventional treatments such as surgery, radiotherapy, and chemotherapy have shown some benefits, but their effectiveness is limited by various factors such as tumor heterogeneity and resistance.

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“…Currently, temozolomide is considered the “gold standard’ chemotherapeutic agent for the treatment of glioblastoma [ 3 , 5 , 13 ]. However, the use of temozolomide is associated with challenges related to resistance development and severe side effects.…”

Section: Introductionmentioning

confidence: 99%

Targeted c-Myc Inhibition and Systemic Temozolomide Therapy Extend Survival in Glioblastoma Xenografts

Dhungel,

Harris,

Romine

et al. 2023

Bioengineering

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Glioblastoma is a highly aggressive disease with poor patient outcomes despite current treatment options, which consist of surgery, radiation, and chemotherapy. However, these strategies present challenges such as resistance development, damage to healthy tissue, and complications due to the blood–brain barrier. There is therefore a critical need for new treatment modalities that can selectively target tumor cells, minimize resistance development, and improve patient survival. Temozolomide is the current standard chemotherapeutic agent for glioblastoma, yet its use is hindered by drug resistance and severe side effects. Combination therapy using multiple drugs acting synergistically to kill cancer cells and with multiple targets can provide increased efficacy at lower drug concentrations and reduce side effects. In our previous work, we designed a therapeutic peptide (Bac-ELP1-H1) targeting the c-myc oncogene and demonstrated its ability to reduce tumor size, delay neurological deficits, and improve survival in a rat glioblastoma model. In this study, we expanded our research to the U87 glioblastoma cell line and investigated the efficacy of Bac-ELP1-H1/hyperthermia treatment, as well as the combination treatment of temozolomide and Bac-ELP1-H1, in suppressing tumor growth and extending survival in athymic mice. Our experiments revealed that the combination treatment of Bac-ELP1-H1 and temozolomide acted synergistically to enhance survival in mice and was more effective in reducing tumor progression than the single components. Additionally, our study demonstrated the effectiveness of hyperthermia in facilitating the accumulation of the Bac-ELP1-H1 protein at the tumor site. Our findings suggest that the combination of targeted c-myc inhibitory biopolymer with systemic temozolomide therapy may represent a promising alternative treatment option for glioblastoma patients.

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Highlighted Advances in Therapies for Difficult-To-Treat Brain Tumours Such as Glioblastoma

Cited by 7 publications

References 166 publications

Glioblastoma Therapy: Past, Present and Future

Glioblastoma Therapy: Past, Present and Future

Targeting inflammation in glioblastoma: An updated review from pathophysiology to novel therapeutic approaches

Targeted c-Myc Inhibition and Systemic Temozolomide Therapy Extend Survival in Glioblastoma Xenografts

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