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Anticancer effects of alpelisib on PIK3CA-mutated canine mammary tumor cell lines
Jiah Yeom1, Yoonju Cho1, Seoungyob Ahn1
1Research Institute, VIP Animal Medical Center, Seoul, Republic of Korea.
Abstract:
Canine mammary tumors (CMTs) are commonly observed in old and unspayed female dogs. Recently, dogs have been increasingly spaying at a young age to prevent mammary tumors. These CMTs require extensive local excision and exhibit a high probability of metastasis to the regional lymph nodes and lungs during malignancy. However, the molecular and biological mechanisms underlying CMT development have not been fully elucidated, and research in this area is limited. Therefore, in this study, we established new CMT cell lines by isolating cells from tumor tissues and investigated phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), a target for human breast cancer. PIK3CA mutations were observed at a similar loci as in the human PIK3CA gene in half of all canine samples. Furthermore, we investigated whether alpelisib, a PIK3CA inhibitor approved by the U.S. Food and Drug Administration for human breast cancer treatment, along with fulvestrant, is effective for CMT treatment. Alpelisib exerted stronger anticancer effects on cell lines with PIK3CA mutations than on the wild-type cell lines. In conclusion, we established new CMT cell lines with PIK3CA mutations and confirmed the efficacy of alpelisib for CMT treatment in vitro.
Insights
New canine mammary tumor (CMT) cell lines with PIK3CA mutations were established. The PIK3CA inhibitor alpelisib showed efficacy in treating these canine mammary tumors in vitro.
Area of Science:
- Veterinary Oncology
- Molecular Biology
- Cancer Research
Background:
- Canine mammary tumors (CMTs) are prevalent in unspayed female dogs, often requiring extensive treatment due to high metastasis rates.
- The molecular mechanisms driving CMT development remain poorly understood, limiting targeted therapeutic strategies.
- Current research on CMTs is limited, highlighting the need for novel cell models and therapeutic investigations.
Purpose of the Study:
- To establish new canine mammary tumor (CMT) cell lines for research.
- To investigate the role of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) in CMTs.
- To evaluate the efficacy of alpelisib, a PIK3CA inhibitor, in treating CMTs.
Main Methods:
- Isolation of cells from canine mammary tumor tissues to establish new cell lines.
- Sequencing to identify mutations in the PIK3CA gene within the established CMT cell lines.
- In vitro treatment of CMT cell lines with alpelisib and fulvestrant to assess anticancer effects.
Main Results:
- New CMT cell lines were successfully established, with PIK3CA mutations identified in approximately half of the canine samples.
- PIK3CA mutations were found at loci similar to those in the human PIK3CA gene.
- Alpelisib demonstrated stronger anticancer effects on CMT cell lines harboring PIK3CA mutations compared to wild-type cell lines.
Conclusions:
- The study successfully established novel CMT cell lines harboring PIK3CA mutations.
- The PIK3CA inhibitor alpelisib shows promising efficacy for treating canine mammary tumors in vitro.
- These findings provide a foundation for further investigation into PIK3CA-targeted therapies for canine mammary cancer.
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