The way to precision medicine in gynecologic cancers: The first case report of an exceptional response to alpelisib in a PIK3CA-mutated endometrial cancer

Abstract

Endometrial cancer (EC) is the most common gynecologic cancer in Europe and its prevalence is increasing. EC includes a biological and clinical heterogeneous group of tumors, usually classified as type I (endometrioid) or type II (non-endometrioid) based on the histopathological characteristics. In 2013, a new molecular classification was proposed by The Cancer Genome Atlas (TCGA) based on the comprehensive molecular profiling of EC. Several molecular somatic alterations have been described in development and progression of EC. Using these molecular features, EC was reclassified into four subgroups: POLE ultra-mutated, MSI hypermutated, copy-number low, and copy-number high that correlate with the prognosis. To this regard, it is widely reported that EC has more frequent mutations in the phosphatidylinositol 3-kinase (PI3K) pathway signaling than any other tumor. PIK3CA is the main significant mutated gene after PTEN alterations. Overall, over 90% of endometrioid tumors have activating PI3K molecular alterations that suggests its critical role in the EC pathogenesis. Thus, the dysregulation of PI3K pathway represents an attractive target in EC treatment. Herein, we report a radiological and clinically meaningful response to a selective PIK3 inhibitor in a patient with extensively pre-treated advanced endometrioid EC harboring a somatic activating PIK3CA hotspot mutation. These evidences provide the rational for translational strategies of the PI3K inhibition and could support the clinical usefulness of PIK3CA genotyping in advanced EC. To our knowledge, this is the first clinical case of PIK3CA-mutated EC successfully treated with alpelisib.

A Rare Pathological Phenotype of Endometrioid Serous and Clear-Cell Ovarian Cancer with PIK3CA Mutations in Relation to The Excellent Response of Alpelisib

“…The most common side effects of alpelisib are rash, hyperglycemia, and mucositis, which occurred within the first 6 weeks and were all manageable when the patient used antihistamines as a premedication. A similar exceptional response was reported in the other case, which provides conclusive clinical evidence for the effectiveness of alpelisib in the treatment of EC cancer patients with a PIK3CA mutation [17]. In another study using alpelisib, the objective response rate (ORR) of recurrent/advanced cervical cancer patients carrying the PIK3CA mutation was 33% [27].…”

“…Following PTEN, PIK3CA is the key gene that has been significantly altered. For the treatment of EC, PI3K/mTOR inhibitors, either alone or in combination, are the subject of numerous registered clinical trials [ 17 ].…”

Photodynamic Therapy for Eye, Ear, Laryngeal Area, and Nasal and Oral Cavity Diseases: A Review

“…This affects both cancerous and healthy cells, with the goal of inhibiting the growth of malignant tissues [74] Surgical interventions involve the physical removal of abnormal tissue, offering immediate tumor debulking and potential cure, but may be associated with postoperative complications [75] Selectivity and precision High selectivity for diseased tissues due to the preferential accumulation of photosensitizers. Precise targeting minimizes damage to adjacent normal structures [76] Targets both cancerous and normal tissues, leading to potential collateral damage and adverse effects [77] Provides precision in localizing and removing abnormal tissue but may lead to collateral damage to nearby healthy structures [78] Invasiveness Generally non-invasive, with light delivery through optical fibers.…”