Miransertib and the PI3K/AKT pathway: an emerging therapeutic approach for Proteus syndrome
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Authors
DOI:
https://doi.org/10.37980/im.journal.ggcl.en.20252747Keywords:
Síndrome de Proteus, inhibición de AKT, Miransertib, terapia dirigida, reviewAbstract
Introduction: Proteus syndrome is a rare disorder characterized by progressive tissue overgrowth associated with abnormal activation of the PI3K/AKT pathway, secondary to mutations in AKT1. Current therapeutic options are limited; however, miransertib, a selective AKT inhibitor, has emerged as a potential alternative by blocking the abnormally elevated activity of AKT1, a key mechanism underlying the dysregulated cellular proliferation that characterizes this disease.
Objective: To describe the clinical, radiological, and functional outcomes of patients with Proteus syndrome treated with miransertib, and to evaluate its impact on lesion growth, mobility, and associated symptoms.
Clinical cases: Four patients with Proteus syndrome are presented, including children, adolescents, and young adults, with variable clinical manifestations such as cerebriform connective tissue nevi, osseous overgrowth, musculoskeletal pain, functional limitation, and, in one case, associated neoplastic disease. Patients were treated with individualized miransertib dosing regimens and underwent clinical, functional, and imaging follow-up.
Results: Treatment with miransertib was associated with a deceleration of lesion growth and, in some cases, a reduction in lesion size. Improvements in joint mobility, pain reduction, and stabilization of pulmonary and skeletal complications were also observed. In one patient, a partial tumor response was documented, with resolution of ascites, peritoneal implants, and portal vein thrombosis, achieving complete clinical remission after prolonged follow-up. Adverse effects were generally mild and manageable.
Conclusion: Selective inhibition of the PI3K/AKT pathway with miransertib appears to slow lesion progression and improve function and quality of life in patients with Proteus syndrome, supporting the therapeutic potential of AKT inhibitors. Nevertheless, long-term studies with larger patient cohorts, evaluation of combination therapies, and identification of predictive biomarkers are required to confirm sustained efficacy and safety and to advance toward personalized medicine.
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