Phosphatase and tensin homologue (PTEN) loss and response to phase I trials targeting PI3K/AKT/mTOR pathway in patients with advanced cancer.

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e13018 Background: PTEN loss has been reported in different tumor types and it leads to activation of the PI3K/AKT/mTOR pathway. Patients bearing tumors with PTEN loss may benefit from treatment with drugs targeting PI3K/AKT/mTOR pathway. Methods: Cytoplasmic PTEN protein expression was evaluated by immunohistochemistry using paraffin blocks from patients referred to the Phase I Unit at M. D. Anderson. Loss of PTEN was established when staining was positive in less than 10% of tumor cells. Patients with PTEN loss were selectively treated with regimens containing inhibitors of PI3K-AKT-mTOR pathway. Results: 159 samples from patients with various advanced cancers have been collected for analysis. The most frequent tumor histologies were colorectal (26), melanoma (23), ovarian (22), head and neck squamous cell carcinoma (13), breast (10), endometrial (8), NSCLC (8), and sarcoma (6). PTEN status was available for 61 patients at the time of submission. Twelve (20%) out of the 61 patients had loss of PTEN including endometrial cancer (3 out of 5, 60%), cervical cancer (2 out of 4, 50%), non-small cell lung cancer (1 out of 2, 50%), head and neck squamous cell carcinoma (2 out of 5, 40%), melanoma (3 out of 12, 25%), colon cancer (1 out of 8, 12.5%). Ten patients with PTEN loss are currently being treated on PI3K-AKT-mTOR pathway targeted phase I protocols. Eight patients have already been restaged. Five patients (63%) had tumor regression ranging from -16% to -70%. Two out of 8 (25%) patients have achieved partial response per RECIST criteria. Five out of 8 had stable disease. One patient had progressive disease. PFS for these patients are: +21, +19, +19, +13, +12, +9, +9 and 5 weeks. Conclusions: Preliminary analysis suggests that PTEN loss was detected in 20% of patients with different solid tumors. 63% of patients with PTEN loss had tumor regression when challenged with drugs targeting the PI3K-AKT-mTOR pathway. No significant financial relationships to disclose.

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