What are the targeted therapeutic genes of bosutinib/bosutinib?

Bosutinib is a second-generation tyrosine kinase inhibitor whose core target is closely related to the molecular basis of Philadelphia chromosome-positive chronic myelogenous leukemia (CML). The occurrence of this disease is related to the abnormal activation of the BCR-ABL fusion gene. The abnormal protein encoded by this fusion gene has sustained kinase activity and can drive leukemia cells to proliferate indefinitely and escape normal regulation. Bosutinib exerts its therapeutic effect by interfering with this abnormal signaling pathway.

From a molecular mechanism perspective, bosutinib mainly inhibits the activity of BCR-ABL tyrosine kinase and blocks its downstream transmission of pro-proliferation and anti-apoptotic signals. Compared with early targeted drugs, bosutinib pays more attention to selectivity in molecular structure design, has strong inhibitory ability against ABL kinase, and also has a certain effect on SRC family kinases. This dual inhibitory property makes it possible to maintain efficacy in some patients who are resistant or intolerant to previous treatments.

SRC kinase also plays a role in the migration, survival and microenvironmental adaptation of leukemia cells. Overseas studies believe that bosutinib's regulation of the SRC pathway may help reduce the invasiveness of leukemia cells and delay disease progression. This mechanism is also regarded as one of the differences between it and other similar drugs at the target level.

It should be noted that bosutinib does not target the "switch" of a single gene but rather intervenes in the abnormal signaling network as a whole by affecting multiple related kinase nodes. While this mode of action improves treatment flexibility, it also requires clinical attention to pay more attention to individualized medication strategies. Different patients have different genetic mutation backgrounds and previous treatment histories, and their responses to drugs will also vary.

In general, the core target gene of bosutinib is the BCR-ABL fusion gene and its related signaling pathways, while also taking into account the inhibition of SRC family kinases. This mechanism has established its important position in the treatment of Philadelphia chromosome-positive chronic myelogenous leukemia.

Keyword tags: Bosutinib target, BCR-ABL fusion gene, Bosutinib mechanism of action, tyrosine kinase inhibitor, CML molecular targeting

Reference: https://en.wikipedia.org/wiki/Bosutinib