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Shp2 is a phosphotyrosine phosphatase; its job is to remove phosphates from protein tyrosine residues, aiding and abetting signal communications within cells. But Shp2 has also been shown to promote the growth and survival of many types of cancers.

Indeed, Shp2 is the first identified oncoprotein in the family of tyrosine phosphatases. Oncoproteins are proteins encoded by an oncogene, which can cause the transformation of a cell into a tumour cell is introduced into it. Drugs that inhibit Shp2, the thinking goes, would attack cancer cells in a way different from other therapies, providing new hope for cancer patients.

But in the new study, researchers at the University of California San Diego, led by senior author Gen-Sheng Feng, PhD, professor of pathology in the UC San Diego School of Medicine and of molecular biology in the Division of Biological Sciences, reveal a previously unrealized complexity in cancer development, one that raises concerns and caution about targeting Shp2 in oncological treatments.

"Targeting Shp2 as a therapy appears to actually worsen the disease, at least in the case of Myc-driven hepatocellular carcinoma (HCC) or liver cancer," said Feng. Myc is a commonly detected oncogene, a mutated form of a gene that can cause the growth of cancer cells.

"This finding will have a profound impact in the cancer field, as both the pharmaceutical industry and research labs are putting huge efforts and resources into searching for and making chemical compounds to target Shp2. We believe a new, effective therapeutic strategy must address the secondary tumour-promoting microenvironment generated in response to the primary (Shp2) targeting compound."

HCC is the most common type of primary liver cancer and the sixth most common type of cancer in the world. It is also among the deadliest. The overall prognosis for survival is grim, with a five-year relative survival rate of just 18.4 per cent. The causes and progressions of HCC are multifactorial, complex, and poorly understood. Treatment is difficult and limited, making it increasingly urgent to find new therapies.

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