Abstract
TSC-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, nab-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 TSC-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 nab-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 nab-sirolimus in these patients, with no standard-of-care treatment options.
Original language | English (US) |
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Article number | 1046442 |
Journal | Frontiers in Oncology |
Volume | 13 |
DOIs | |
State | Published - Feb 9 2023 |
Keywords
- gemcitabine
- mTOR - mammalian target of rapamycin
- nab-sirolimus
- PEComa
- sarcoma
- TSC
ASJC Scopus subject areas
- Oncology
- Cancer Research