Indications for Dasatinib/Startase

Dasatinib (Dasatinib) is a potent multi-target tyrosine kinase inhibitor and a second-generation BCR-ABL inhibitor. Its unique feature is that it not only inhibits BCR-ABL mutants (including some imatinib-resistant mutations), but also acts on multiple kinases such as SRC, c-KIT and PDGFR, giving it a wider range of indications in the treatment of leukemia.

Currently, dasatinib is widely used to treat Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Dasatinib has been established as one of the first-line treatment options for newly diagnosed adult patients in the chronic phase of CML; for patients who have previously received imatinib but developed resistance or intolerance, it also shows significant molecular response rates and faster hematological remissions.

In addition to adults, dasatinib is also approved for the treatment of Ph+ CML chronic phase and Ph+ ALL in pediatric patients 1 year old and above. It is especially suitable for newly diagnosed or relapsed and refractory cases. Studies have shown that after pediatric patients received dasatinib combined with chemotherapy, the disease remission rate was significantly accelerated and the control rate of central nervous system leukemia was improved. This is closely related to the good blood-brain barrier penetration of the drug.

In addition, dasatinib has shown unique advantages in some drug-resistant complex mutant leukemias. Because it binds the active and inactive conformations ofBCR-ABL kinase, it is still effective against mutants that cannot be inhibited by imatinib. It is worth noting that despite their broad effects, other TKI alternatives such as bosutinib or alotinib still need to be considered for patients with T315I mutations.

The indications of dasatinib are still being expanded, and some studies are exploring its application in combination immunotherapy and other hematological tumors, such as its combination withPD-1 inhibitors to improve the long-term survival of relapsed Ph+ ALL.

Reference materials:https://go.drugbank.com/drugs/DB01254