XP-102 holds potential as an innovative therapy against B-RAF
V600 mutated solid tumors including CRC and non-small cell lung cancer and hairy cell leukemia.
Jazz said Redx has the potential to work in RAF driven tumors where current selective B-RAF
inhibitors and their respective combinations are ineffective due to acquired resistance mechanisms.
The pan-RAF inhibitor programme aims to overcome resistance mechanisms associated with clinically approved B-RAF
MapKure intends to develop BGB-3245, an investigational, oral, selective small molecule inhibitor of monomer and dimer forms of activating B-RAF
mutations including V600 BRAF mutations, non-V600 B-RAF
mutations, and RAF fusions.
In our laboratory, the AmpliSeq Cancer Hotspot panel v2 (Thermo Fischer Scientific, Waltham, Massachusetts) is used with the Ion Torrent Personal Genome Machine (Life Technologies, Grand Island, New York) to detect mutations in several hot spot regions in 50 oncogenes and tumor suppressor genes; currently, we only report mutations in EGFR, Kirsten rat sarcoma viral oncogene homolog (KRAS), and B-Raf
proto oncogene (BRAF) on clinical samples (Figure 3).
This misreading of signals appears to occur because of a specific type of mutation in the protein B-Raf
corrupts the timing of incoming growth signals, the researchers found, causing short pulses of Ras activation to reverberate for longer within an affected cell - similar to how the 'sustain' pedal on a piano causes individual notes to be drawn out and blur together.
 Human Genes: KRAS, KRAS proto-oncogene; NRAS, NRAS proto-oncogene; BRAF, B-Raf
proto-oncogene; MLH1, mutLhomolog 1; PMS2, PMS1 homolog 2.
RAF kinases are of three types- A-RAF, B-RAF
(BRAF), and C-RAF out of which BRAF is the most potent activator of the MAP kinase pathway.
gene, located on chromosome 7q34, encodes B-RAF
serine-threonine kinase, which functions as an intracellular effector of the RAS/MAPK signaling cascade (Figure 1).
Roe et al., "Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF
," Cell, vol.
MEK1 mutations confer resistance to MEK and B-RAF
He had a history of B-Raf
proto-oncogene, serine/threonine kinase (BRAF)-positive metastatic melanoma with unknown primary and metastasis to the inguinal fossa and right thigh diagnosed two years previously.