How does Dabrafenib actually work to inhibit?

Dabrafenib (Tafinlar) belongs to a class of drugs known as protein kinase inhibitors. It works by blocking the function of an abnormal form of a protein called BRAF. The RAF proteins were discovered through studies of viruses that cause cancer in mice.

Can you prevent hairy cell leukemia?

Become educated on how you can prevent and reduce your risk of hairy cell leukemia innovative screening methods at the OSUCCC – James. Exposure to certain chemicals such as those used in farming may increase the risk of developing HCL.

How does BRAF inhibitor work?

The BRAF inhibitors vemurafenib, dabrafenib and encorafenib are used in the treatment of patients with BRAF-mutant melanoma. They selectively target BRAF kinase and thus interfere with the mitogen-activated protein kinase (MAPK) signalling pathway that regulates the proliferation and survival of melanoma cells.

What is the most common adverse event reported with vemurafenib in patients with hairy cell leukemia HCL )?

Leukemic hairy cells accumulate in the bone marrow and cause pancytopenia, which is the most common finding at initial presentation. HCL patients report symptoms of fatigue, infections, and, occasionally, left-sided abdominal pain caused by splenomegaly.

Which is the best BRAF inhibitor for leukemia?

Low doses of the BRAF inhibitor vemurafenib are highly effective in refractory hairy cell leukemia. Abrogation of BRAF V600E–induced signaling was consistently seen with 240 mg of vemurafenib twice daily.

Are there any mutations in the BRAF gene?

In vitro incubation of BRAF-mutated primary leukemic hairy cells from 5 patients with PLX-4720, a specific inhibitor of active BRAF, led to a marked decrease in phosphorylated ERK and MEK. The BRAF V600E mutation was present in all patients with HCL who were evaluated.

How is plx-4720 used to treat leukemic hairy cells?

In vitro incubation of primary leukemic hairy cells from five additional patients with the specific active BRAF inhibitor PLX-4720 led to a marked decrease in phosphorylated MEK and ERK at low drug concentrations (≤1 μM), whereas vehicle-treated cells retained MEK and ERK phosphorylation (Figure 3B).

Which is the key mutation in hairy cell leukemia?

The activating mutation of the BRAF serine/threonine protein kinase (BRAF V600E) is the key driver mutation in hairy cell leukemia (HCL), suggesting opportunities for therapeutic targeting.