Shp2: Potential star anti-cancer targets may promote cancer?

Shp2 can be described as an emerging star anti-cancer drug target in recent years.

Although scientists believe that drugs that inhibit Shp2 can attack cancer cells in a different way than other therapies, providing cancer patients with new hope

In this study, the researchers mainly explored the main mechanism of Shp2 in Myc-driven hepatocellular carcinoma (hepatocellular carcinoma, HCC)

So, what impact will Shp2 and Myc have on hepatocellular carcinoma? By creating genetically engineered mouse models and performing single-cell RNA sequencing, researchers have explored the possibility of whether Shp2 can become a new target for cancer treatment

In this study, researchers transfected human Myc (hMyc) and Sleeping Beauty (SB) transposases into wild-type (WT) and hepatocyte-specific Shp2 knockout mice (SKO).

So, how does Shp2 promote the progression of Myc-induced hepatocellular carcinoma? The researchers analyzed the underlying mechanism of the aggressive HCC phenotype with single-cell resolution, established a unique liver tissue processing protocol, and used scRNA-seq to analyze stem cell types

With the new findings, the researchers asked more in-depth questions, why does Myc-driven HCC strictly require Shp2? Studies have shown that Shp2 has an activating effect on the Ras-Erk-Myc signaling pathway, which leads to the autonomic requirements of the Shp2 gene in Myc-driven tumors being covered by the oncogenic Ras mutant co-transfected with Myc.

Overall, the study found that tumor cells need Shp2 to accelerate the development of HCC, which validates and strengthens the theory that Shp2 is a new ideal target for cancer treatment, but at the same time, removing Shp2 from liver cells can also make Myc carcinogenic.

Facing this contradictory research result, Professor Feng, one of the research team members, pointed out: “These unexpected results may help understand tumor recurrence, which is also the main cause of death of most cancer patients

From non-preparable drugs to star targets, many companies have already deployed to rush away

The Cell Reports study allowed us to see the contradiction of the Shp2 target, and it also sounded the alarm for the research and development of SHP2 inhibitors by pharmaceutical companies, but its potentially superior anti-cancer properties still drive many pharmaceutical companies to carry out this The layout of the track

Among foreign pharmaceutical companies, Novartis, Sanofi, Roche, BMS, Merck, AbbVie and other companies have taken the lead

Sanofi, Roche, and BMS have chosen the way of R&D cooperation to seize the SHP2 track

In China, pharmaceutical companies such as Nuocheng Jianhua, Yituo Pharmaceutical, Jakosi, Betta Pharmaceuticals, Shenghe Pharmaceuticals, and Qinhao Pharmaceutical have taken the lead

Jacos currently has two SHP2 targeted small molecule inhibitors under development, namely JAB-3068 and JAB-3312

From the current clinical developments, it can be seen that the research and development of SHP2 inhibitors by domestic and foreign pharmaceutical companies are in the clinical stage, and the research and development of the drug is also more inclined to cooperate and develop together as a target that has always been considered "difficult to make a drug".

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