Bruton's tyrosine kinase as anti-cancer drug target

摘要

Receptor protein kinases (RPTKs) transmit extracellular signals across the plasma membrane to cytosolic proteins, stimulating formation of complexes that regulate key cellular functions. Over half of the known tyrosine kinases are implicated in human cancers and are therefore highly promising drug targets. A large-scale loss-of-function analysis of tyrosine kinases using RNA interference in the clinically relevant Erb-B2 positive, BT474 breast cancer cell line showed that Bruton's tyrosine kinase (BTK), a cytosolic, non-receptor tyrosine kinase that has been extensively studied for its role in B cell development, is required, in altered form, for BT474 breast cancer survival. This alternative form contains an amino-terminal extension that is also present in tumorigenic breast cells at significantly higher levels than in normal breast cells.

主权项

1. A method of treating cancer, comprising:
a) providing:
i) subject with breast cancer,ii) a chemotherapeutic agent, andiii) an inhibitor of a gene encoding a cytoplasmic tyrosine kinase, wherein said inhibitor comprises an interfering double stranded RNA selected from the group consisting of: sense strand having the nucleotide sequence of SEQ ID NO: 66, an antisense strand having the nucleotide sequence of SEQ ID NO: 67, a sense strand having the nucleotide sequence of SEQ ID NO: 68, and an antisense strand having the nucleotide sequence of SEQ ID NO: 69; and b) treating said subject with said chemotherapeutic agent and said inhibitor.