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Patients with HCC, SALL4 oncofetal gene require targeted therapy
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The oncofetal gene SALL4 plays a key role in the heterogeneous cellular pathways underlying hepatocarcinogenesis in patients with hepatocellular carcinoma, study results showed.
The researchers propose that a 12-amino acid peptide that blocks the oncogenic role of SALL4 may have therapeutic potential in SALL4-positive hepatocellular carcinoma and therefore increase OS in this patient population.
Despite the well-known risk factors for hepatocellular carcinoma, the molecular mechanisms underlying hepatocarcinogenesis are not well characterized, according to researchers.
“Hepatocellular carcinomas with characteristics of embryonic stem-cell and progenitor-cell gene expression are associated with the worst prognosis,” they wrote. “The oncofetal gene SALL4, a marker of a subtype of hepatocellular carcinoma with progenitor-like features, is associated with a poor prognosis and is a potential target for treatment.”
For this reason, the researchers assessed tumor tissue specimens from 400 patients for the expression of SALL4 from patients with primary hepatocellular carcinoma. They then performed loss-of-function studies to evaluate the role of SALL4 in hepatocarcinogenesis and its potential as a molecular target for therapy.
Results indicated that between 10% and 20% of patients expressed high levels of SALL4, and 50% of patients expressed low levels of SALL4. Therefore, the researchers suggest SALL4 is an independent marker for HCC prognosis and that patients with this gene should be treated with a more aggressive regimen.
In addition to this finding, the investigators also found that SALL4 was “switched off” when a therapeutic peptide was used, which led to the blocking of the tumor-forming ability of the cancer cells.
These findings may lead to the development of personalized treatments and targeted therapeutics for HCC, as well as contribute toward improving the treatment of other types of cancers such as leukemia, and ovarian, endometrial, gastric, breast and lung cancers, researchers said.
Disclosure: This study was funded by the Singapore National Medical Research Council, as well as by grants from the NIH and the Singapore Ministry of Education and National Research Foundation.
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