Published : Jan. 3, 2025.
The study investigates the potential factors that might lead to dysregulation of PI3K/AKT signaling pathways in canine tumors. These factors include the loss of PTEN, PIK3CA mutation, and EGFR over-expression. By understanding the distinct contributions and interactions of each component, researchers can gain valuable insights that might help identify potential biomarkers for early detection and uncover novel therapeutic targets.
PTEN mutations or deletions in dogs result in aberrations in the PI3K/AKT signaling pathway, contributing to tumorigenesis. Previous studies in canine hemangiosarcoma, osteosarcoma, and canine mammary tumor showed that these malignancies frequently exhibit PTEN loss or reduced expression. However, this study did not detect PTEN loss, as the expression of PTEN in samples does not necessarily ensure that this tumor suppressor gene is functioning correctly.
The study also identified mutations in the PIK3CA gene that can drive the dysregulation of the PI3K/AKT pathway. Exon 10 and exon 21 mutations were identified in canine HSA, OS, and CMT, with a prevalence of 12.5%. This discrepancy in prevalence may be attributed to a limited number of samples analyzed.
The presence of a mutation in EGFR leads to continuous activation of downstream signaling pathways, such as the PI3K/AKT pathway, the RAS/RAF/MEK/ERK, and the JAK/STAT pathways. One out of 12 samples (8.3%) had an EGFR mutation in exon 21. The mutation analysis of PIK3CA and EGFR in this study offers additional insights into the genetic alterations associated with canine cancer and aberrant PI3K/AKT signaling pathways.
The findings indicate that PTEN weak expression and EGFR strong expression levels were significantly associated with high grade tumors. A positive correlation between EGFR expression and phospho-AKT suggests that EGFR is likely driving the activation of the PI3K/AKT pathway, which highlights the importance of EGFR and PI3K/AKT signaling in canine soft tissue sarcoma progression and may inform targeted therapeutic strategies in the future.