Dasatinib (brand name Sprycel) is a a tyrosine-kinase inhibitor medication used to treat certain cases of chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL). Specifically it is used to treat cases that are Philadelphia chromosome-positive (Ph+).
Dasatinib was approved for medical use in the United States and in the European Union in 2006.
The main targets of dasatinib are BCR/Abl (the “Philadelphia chromosome”), Src, c-Kit, ephrin receptors, and several other tyrosine kinases1. Strong inhibition of the activated BCR-ABL kinase distinguishes dasatinib from other CML treatments, such as imatinib and nilotinib. Although dasatinib only has a plasma half-life of three to five hours, the strong binding to BCR-ABL1 results in a longer duration of action.
Dasatinib Side Effects
The most common side effects are infection, suppression of the bone marrow (decreasing numbers of leukocytes, erythrocytes, and thrombocytes), headache, hemorrhage (bleeding), pleural effusion (fluid around the lungs), dyspnea (difficulty breathing), diarrhea, vomiting, nausea, abdominal pain, skin rash, musculoskeletal pain, tiredness, swelling in the legs and arms and in the face, fever. Neutropenia and myelosuppression were common toxic effects.
Fifteen people (of 84, i.e. 18%) in one study2 developed pleural effusions, which was a suspected side effect of dasatinib. Some of these people required thoracentesis or pleurodesis to treat the effusions.
Other adverse events included mild to moderate diarrhea, peripheral edema, and headache. A small number of people developed abnormal liver function tests which returned to normal without dose adjustments.
Mild hypocalcemia was also noted, but did not appear to cause any significant problems. Several cases of pulmonary arterial hypertension (PAH) were found in people treated with dasatinib, possibly due to pulmonary endothelial cell damage3.
Research
Dasatinib was developed by collaboration of Bristol-Myers Squibb and Otsuka Pharmaceutical Co., Ltd, and named for Bristol-Myers Squibb research fellow Jagabandhu Das, whose program leader says that the drug would not have come into existence had he not challenged some of the medicinal chemists’ underlying assumptions at a time when progress in the development of the molecule had stalled.
It has been shown to eliminate senescent cells in cultured adipocyte progenitor cells4. Dasatinib has been shown to induce apoptosis in senescent cells by inhibiting Src kinase, whereas quercetin inhibits the anti-apoptotic protein Bcl-xL. Administration of dasatinib along with quercetin to mice improved cardiovascular function and eliminated senescent cells. Aged mice given dasatinib with quercetin showed improved health and survival.
- Piscitani L, Sirolli V, Morroni M, Bonomini M (2020). Nephrotoxicity Associated with Novel Anticancer Agents (Aflibercept, Dasatinib, Nivolumab): Case Series and Nephrological Considerations. International Journal of Molecular Sciences. 21 (14): e4878 ↩︎
- Olivieri, A.; Manzione, L. (2007). Dasatinib: a new step in molecular target therapy. Annals of Oncology. 18 Suppl 6: vi42–vi46. ↩︎
- Yurttaş NO, Eşkazan AE (2018). Dasatinib-induced pulmonary arterial hypertension. British Journal of Clinical Pharmacology. 84 (5): 835–845. ↩︎
- Kirkland JL, Tchkonia T (2020). Senolytic drugs: from discovery to translation. Journal of Internal Medicine. 288 (5): 518–536. ↩︎
Last Updated on October 26, 2022