AUTHOR=Nassif Elise F. , Joseph Cissimol P. , Lazcano Rossana , Joseph Jocelyn T. , Thirasastr Prapassorn , Lazar Alexander J. , Somaiah Neeta 

TITLE=Case report: Responses to the combination of gemcitabine with sirolimus in two patients with TSC-mutated sarcomas

JOURNAL=Frontiers in Oncology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1046442

DOI=10.3389/fonc.2023.1046442

ISSN=2234-943X

ABSTRACT=<p><italic>TSC</italic>-mutated sarcomas are rare molecular and histologic types of sarcoma. Due to the presence of their specific oncogenic driver mutation, these sarcomas are particularly sensitive to mTOR inhibitors. Recently, <italic>nab</italic>-sirolimus, an albumin-bound mTOR inhibitor, was approved by the Food and Drug Administration (FDA) for PEComas, which harbor a TSC mutation, and this drug remains the only FDA-approved systemic treatment for these tumors. We report on two cases of patients with <italic>TSC</italic>-mutated sarcomas who experienced significant responses to the combination of gemcitabine and sirolimus, after progression on prior gemcitabine-based chemotherapy and single agent mTOR inhibition with <italic>nab</italic>-sirolimus. Preclinical and clinical data support rationale for a synergistic effect of the combination. This combination may represent a valid therapeutic option after failure of <italic>nab</italic>-sirolimus in these patients, with no standard-of-care treatment options.</p>