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Identification of novel therapeutic targets in the PI3K/AKT/mTOR pathway in hepatocellular carcinoma using targeted

Filip Janku1, Ahmed O Kaseb, Apostolia M Tsimberidou

  • 1Departments of Investigational Cancer Therapeutics. Phase I Clinical Trials Program.

Oncotarget
|June 17, 2014
PubMed

Insights

Genomic alterations are frequent in advanced hepatocellular carcinoma (HCC). Patients with PI3K/AKT/mTOR pathway aberrations showed promising responses to mTOR inhibitors, suggesting new therapeutic avenues for refractory HCC.

Area of Science:

  • Oncology
  • Genomics
  • Molecular Biology

Background:

  • Hepatocellular carcinoma (HCC) is a significant global health challenge.
  • The genomic landscape of advanced and metastatic HCC remains incompletely understood.
  • Identifying novel therapeutic targets is crucial for improving outcomes in refractory HCC patients.

Observation:

  • Targeted next-generation sequencing (NGS) was performed on tumor samples from 14 patients with advanced/metastatic HCC.
  • Molecular abnormalities were detected in 12 out of 14 patients, with a median of 2 aberrations per patient.
  • Commonly altered pathways included PI3K/AKT/mTOR, Wnt, and MAPK, alongside disruptions in DNA repair, cell cycle control, and apoptosis.

Findings:

  • Three patients with molecular aberrations putatively activating the PI3K/AKT/mTOR pathway were identified.
  • Two of these patients received mTOR inhibitor therapy.
  • Both patients treated with mTOR inhibitors demonstrated therapeutic benefit, including partial response and minor tumor shrinkage.

Implications:

  • Genomic alterations are prevalent in advanced HCC, offering potential targets for treatment.
  • Patients with PI3K/AKT/mTOR pathway aberrations may benefit from mTOR-targeted therapies.
  • These findings support further investigation of mTOR inhibitors in refractory HCC with specific molecular alterations.

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