Reference Detail

Ref Type

PMID

(36713525)

Authors

Passarelli A, Ventriglia J, Pisano C, Cecere SC, Napoli MD, Rossetti S, Tambaro R, Tarotto L, Fiore F, Farolfi A, Bartoletti M, Pignata S

Title

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

Journal	Vol	Issue	Date	Pages	Journal Short Title
Frontiers in oncology	12		2022	1088962	Front Oncol

URL

Abstract Text

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.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance
ROS1	G1027D	missense	unknown	ROS1 G1027D lies within fibronectin type-III domain 4 of the Ros1 protein (UniProt.org). G1027D has been identified in sequencing studies (PMID: 32504289, PMID: 36713525), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024).

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
PIK3CA H1047R	endometrial cancer	predicted - sensitive	Alpelisib	Case Reports/Case Series	Actionable	In a clinical case study, Piqray (alpelisib) resulted in a partial response after 4 months in a patient with endometrial endometrioid cancer harboring PIK3CA H1047R, with treatment ongoing at 7 months (PMID: 36713525).	36713525