Uttroside B, a US FDA-designated ‘Orphan Drug’, mitigates the development of hepatocellular carcinoma and its pulmonary metastasis via EGFR/ERK-mediated inhibition of SREBP-1 and STAT-3

Cancer research · Hepatocellular carcinoma · EGFR · BRAF

Uttroside B shows potent anti‑hepatocellular carcinoma (HCC) activity and blocks pulmonary metastasis by inhibiting the EGFR/ERK/SREBP‑1 signalling axis, leading to reduced tumour growth and invasion.

Hepatocellular carcinoma (HCC) is a highly aggressive tumour with a high propensity for extra‑hepatic metastasis and poor long‑term survival with current therapies. We investigated the mechanism and therapeutic potential of Uttroside B (Utt‑B) using in‑vitro, in‑vitro, and in‑vivo models. In HepG2 cells, Utt‑B down‑regulated key oncogenic signalling pathways – EGFR, MAPK/ERK, mTOR – and downstream effectors SREBP‑1 and STAT‑3, leading to cytotoxicity, apoptosis and inhibition of invasion. In an orthotopic xenograft model, Utt‑B reduced primary liver tumour burden and diminished pulmonary metastasis via suppression of EGFR/ERK signalling. These findings support Utt‑B as a candidate drug for early‑phase clinical evaluation in HCC patients with limited treatment options.

Effective systemic control of HCC and its common lung metastases remains a major unmet need. A compound that targets critical signalling pathways (EGFR/ERK/STAT‑3) and demonstrates both anti‑tumour and anti‑metastatic activity offers a promising therapeutic avenue that could improve survival and quality of life in HCC patients.

Evidence level: Sejtvonalas. Laboratóriumi sejtekben vizsgálták.

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