# Redundancy in Growth Factor Receptor Signaling in Adult Astrocytoma Resistance to Small-Molecule Tyrosine Kinase Inhibitors

**Authors:** Roxana Radu, Anica Dricu, Ligia Gabriela Tataranu, Oana Alexandru

PMC · DOI: 10.3390/ijms27031196 · International Journal of Molecular Sciences · 2026-01-24

## TL;DR

This review explores why adult astrocytomas resist tyrosine kinase inhibitors, focusing on growth factor receptor signaling and resistance mechanisms.

## Contribution

The paper reviews redundancy in growth factor receptor signaling as a novel resistance mechanism in adult astrocytomas.

## Key findings

- Growth factor receptors and their signaling pathways are key in adult astrocytoma biology.
- Resistance mechanisms to tyrosine kinase inhibitors remain complex and poorly understood.
- Tumor heterogeneity contributes to robust drug resistance in these gliomas.

## Abstract

Adult astrocytomas, particularly IDH1/IDH2-wildtype infiltrating astrocytic gliomas, represent a significant challenge for medical professionals. Despite recent progress in understanding tumor biology and the use of molecular biomarkers, therapeutic options have not significantly improved patient outcomes. Although targeted therapies, such as small-molecule tyrosine kinase inhibitors (TKIs), have shown benefits in other solid tumors, they have largely failed to improve survival in adult astrocytoma patients. Characterized by remarkable heterogeneity, these tumors develop robust drug resistance mechanisms. The molecular processes driving this resistance are complex and not yet fully understood. In this review, we briefly present the growth factor receptors (GFRs) and their signaling pathways in adult astrocytomas and discuss the known mechanisms of resistance to small-molecule tyrosine kinase inhibitors.

## Linked entities

- **Genes:** IDH1 (isocitrate dehydrogenase (NADP(+)) 1) [NCBI Gene 3417], IDH2 (isocitrate dehydrogenase (NADP(+)) 2) [NCBI Gene 3418]

## Full-text entities

- **Genes:** IDH1 (isocitrate dehydrogenase (NADP(+)) 1) [NCBI Gene 3417] {aka HEL-216, HEL-S-26, IDCD, IDH, IDP, IDPC}, IDH2 (isocitrate dehydrogenase (NADP(+)) 2) [NCBI Gene 3418] {aka D2HGA2, ICD-M, IDH, IDH-2, IDHM, IDP}
- **Diseases:** tumor (MESH:D009369), Astrocytoma (MESH:D001254)
- **Chemicals:** Small-Molecule Tyrosine Kinase (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

259 references — full list in the complete paper: https://tomesphere.com/paper/PMC12897831/full.md

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Source: https://tomesphere.com/paper/PMC12897831