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Ref Type Journal Article
PMID (31058421)
Authors Leoni C, Gullo G, Resta N, Fagotti A, Onesimo R, Schwartz B, Kazakin J, Abbadessa G, Crown J, Collins CD, Ranieri C, Scambia G, Zampino G
Title First evidence of a therapeutic effect of miransertib in a teenager with Proteus syndrome and ovarian carcinoma.
Journal Vol Issue Date Pages Journal Short Title
American journal of medical genetics. Part A 179 7 2019 07 1319-1324 Am J Med Genet A
URL
Abstract Text Proteus syndrome (PS) is an ultra-rare disease characterized by progressive, disproportionate, segmental overgrowth caused by a somatic gain-of-function mutation p.Glu17Lys in the oncogene AKT1. The disease has high morbidity and mortality rates due to the increased risk for patients to develop cancer and progressive overgrowth. A teenage patient with severe PS phenotype developed a pelvic recurrence of low-grade serous ovarian carcinoma (LGSOC). Taking into consideration, recent results of the use of AKT inhibitors both in PS and AKT-mutant cancers, we treated the patient on a compassionate basis, with miransertib (ARQ 092), a potent, selective, allosteric AKT inhibitor. Targeted deep sequencing assay of PI3K/AKT pathway genes of the affected overgrowth lesion (cerebriform connective tissue nevus) and the tumor tissues detected the same activating AKT1 mutation in both. Treatment with miransertib led to a complete remission of the cancer and a significant improvement in the patients' everyday life. The treatment is still ongoing at 22 months. This is the first report showing the therapeutic effects of an AKT inhibitor on both benign and malignant tissues that harbor the same pathogenic AKT1 mutation. The present article showed that personalized medicine is feasible in ultra-rare diseases.

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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
Miransertib Miransertib 22 2
Drug Name Trade Name Synonyms Drug Classes Drug Description
Miransertib ARQ-092|ARQ092|ARQ 092 Akt Inhibitor (Pan) 21 Miransertib (ARQ092) is a pan-AKT inhibitor, resulting in inhibition of the PI3K/AKT signaling pathway and cell proliferation (PMID: 26469692, PMID: 31058421).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References