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PIK3CA Mutations: Are They a Relevant Target in Adult Diffuse Gliomas?
Ana Tomás1,2, Marta Pojo1
1Unidade de Investigação em Patobiologia Molecular (UIPM), Instituto Português de Lisboa Francisco Gentil (IPOLFG) E.P.E., 1099-023 Lisbon, Portugal.
Abstract:
Gliomas are the most common and lethal malignant primary brain tumors in adults, associated with the highest number of years of potential life lost. The latest WHO classification for central nervous system tumors highlighted the need for new biomarkers of diagnosis, prognosis, and response to therapy. The PI3K/Akt signaling pathway is clearly implicated in tumorigenesis, being one of the most frequently altered pathways in cancer. Activating PI3KCA mutations are oncogenic and can influence both prognosis and treatment response in various tumor types. In gliomas, however, studies have reported inconsistent PIK3CA mutational frequencies, ranging from 0% to 30%. Furthermore, the impact of these alterations on glioma diagnosis, prognosis, and therapy response remains unclear. Current evidence suggests that PIK3CA mutations may represent early and constitutive events in glioma development, associated with worse glioblastoma prognoses, earlier recurrences, and widespread disease. Among these, the hotspot mutation H1047R has been particularly associated with a more aggressive phenotype while also modulating the neuronal microenvironment. In this review, we examine the clinical relevance of PIK3CA mutations across different cancers, with a particular focus on their emerging role in glioma. Moreover, we also discuss the therapeutic potential and challenges of targeting PIK3CA mutations in the context of glioma.
Insights
Activating PIK3CA mutations in brain gliomas are linked to aggressive disease and poor prognosis. Targeting these mutations offers potential therapeutic strategies for glioma patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gliomas are aggressive primary brain tumors with poor outcomes.
- The PI3K/Akt pathway is crucial in cancer development, with PIK3CA mutations frequently observed.
- Inconsistent PIK3CA mutation frequencies and unclear clinical impact in gliomas necessitate further investigation.
Purpose of the Study:
- To review the clinical relevance of PIK3CA mutations in various cancers, focusing on gliomas.
- To elucidate the role of PIK3CA mutations in glioma diagnosis, prognosis, and treatment response.
- To discuss therapeutic strategies targeting PIK3CA mutations in glioma.
Main Methods:
- Literature review of studies on PIK3CA mutations in cancer, particularly gliomas.
- Analysis of current evidence regarding the impact of PIK3CA mutations on glioma characteristics.
- Examination of therapeutic approaches targeting PIK3CA.
Main Results:
- PIK3CA mutations are oncogenic and affect prognosis and treatment response in multiple cancers.
- PIK3CA mutations in gliomas may be early events associated with worse glioblastoma prognosis, earlier recurrence, and widespread disease.
- The hotspot mutation H1047R is linked to a more aggressive glioma phenotype and modulation of the neuronal microenvironment.
Conclusions:
- PIK3CA mutations play a significant role in glioma development and progression.
- Understanding PIK3CA alterations is critical for improving glioma diagnosis and prognosis.
- Targeting PIK3CA mutations presents a promising therapeutic avenue for glioma treatment, despite existing challenges.
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