Targeting Src Family Kinases in Glioblastoma Therapeutics

Glioblastoma multiforme is the most aggressive primary brain tumour in adults, displaying marked heterogeneity, invasive growth and resistance to conventional therapies. Aberrant activation of Src family kinases, a group of non-receptor tyrosine kinases, contributes to tumour cell proliferation, migration, angiogenesis and survival through multiple downstream effectors. Inhibiting these kinases offers a dual advantage: direct attenuation of oncogenic signalling and sensitisation to radiation or chemotherapy. Preclinical models have shown that targeted Src inhibition can reduce invasive front dynamics, disrupt tumour–stroma crosstalk and overcome adaptive resistance driven by hypoxia. Optimised small-molecule inhibitors derived from pyrazolo[3,4-d]pyrimidine scaffolds demonstrate potent enzymatic blockade, favourable blood–brain barrier permeability and synergistic efficacy when combined with temozolomide or proton beam therapy. Collectively, these findings underscore the global significance of Src family kinase targeting as a promising adjunct in glioblastoma treatment paradigms.

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Targeting Src Family Kinases in Glioblastoma Therapeutics publication trend

The graph below shows the total number of articles in targeting src family kinases in glioblastoma therapeutics across all publications each year (not limited to Nature Index journals).

Technical terms

Src Family Kinases: A group of intracellular non-receptor tyrosine kinases that regulate cell proliferation, adhesion, migration and survival.

Tyrosine Kinase Inhibitors (TKIs): Small molecules that bind to the ATP pocket of kinases, blocking phosphorylation events and downstream signalling.

Glioblastoma Multiforme: The most malignant primary brain tumour in adults, characterised by rapid growth, invasiveness and poor prognosis.

Blood–Brain Barrier (BBB): A highly selective endothelial interface that limits entry of most circulating substances into the central nervous system.

References

1. Biological Evaluation and In Vitro Characterization of ADME Profile of In-House Pyrazolo[3,4-d]pyrimidines as Dual Tyrosine Kinase Inhibitors Active against Glioblastoma Multiforme. Pharmaceutics (2023).
2. Identification and Biological Characterization of the Pyrazolo[3,4-d]pyrimidine Derivative SI388 Active as Src Inhibitor. Pharmaceuticals (2023).
3. The Hallmarks of Glioblastoma: Heterogeneity, Intercellular Crosstalk and Molecular Signature of Invasiveness and Progression. Biomedicines (2022).
4. The Role of Hypoxia and SRC Tyrosine Kinase in Glioblastoma Invasiveness and Radioresistance. Cancers (2020).
5. SRC Kinase in Glioblastoma: News from an Old Acquaintance. Cancers (2020).
6. Suppression of SRC Signaling Is Effective in Reducing Synergy between Glioblastoma and Stromal Cells. Molecular Cancer Therapeutics (2016).
7. Proton Therapy and Src Family Kinase Inhibitor Combined Treatments on U87 Human Glioblastoma Multiforme Cell Line. International Journal of Molecular Sciences (2019).