Background: Phosphatidylinositol 3‐kinase (PI3K) is thought to play an important role in tumorigenesis. Activating mutations of the p110 subunit of PI3K (PIK3CA) have been identified in a broad spectrum of tumors.

Methods: A mutational analysis (a PCR‐based DNA sequencing) of exon 9 (helical domain) and exon 20 (kinase domain) of the PIK3CA was performed using DNA obtained from tumors of patients referred for clinical trials using targeted therapy. Patients with PIK3CA were preferably treated whenever possible with regimens containing PI3K‐AKT‐mTOR signaling pathway inhibitors.

Results: To date 146 samples from patients with various advanced cancers have been collected. At the time of submission 117 results from mutational analysis were available (ovarian cancer, n=23; colon cancer, n=13; cervical cancer, n=10; endometrial cancer, n=7; breast cancer, n=11; melanoma, n=7; head and neck cancer, n=10; soft tissue sarcoma [not including GIST] n=6; renal cancer, n=4; and other tumor types, n=26). PIK3CA mutations were detected in 14 (12%) patients (3 in exon 9‐helical domain, 11 in exon 20‐kinase domain). In tumor types with more than 5 patients tested, PIK3CA mutations were most frequent in endometrial cancer (43%, 3 out of 7 patients), ovarian cancer (22%, 5 out of 23 patients), squamous head and neck cancer (14%, 1 out of 7 patients), breast cancer 18% (2 out of 11 patients), and colon cancer (15%, 2 out of 13 patients). No mutations were identified in patients with melanoma or cervical cancer. The small number of patients at this point precludes statistical comparisons. Of the 14 patients with PIK3CA mutations, 10 were treated on a protocol that included a drug targeting the PI3K‐AKT‐mTOR pathway, and 4 (40%) responded (partial responses). Although numbers are small, in individual disease there were 2 (67%) responses in 3 endometrial cancers, 1 (25%) in 4 ovarian cancers, 1 (100%) in 1 breast cancer, and no response in 1 colorectal cancer patient.

Conclusion: PIK3CA mutations were detected in 12% of patients with various solid tumors. Although numbers are small, response rate appears high (40%) in tumors with PIK3CA mutations treated with PI3K‐AKT‐mTOR pathway inhibitors.

Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B134.

Copyright © 2009, American Association for Cancer Research
2009