摘要：Aberrant protein kinase activity promotes tumor survival and proliferation, and targeted kinase inhibitors that halt growth and promote apoptosis demonstrate some cancers are truly kinase addicted. Clinically, this is best exemplified by chronic myeloid leukemia (CML), driven by the fusion kinase BCR-ABL, where tyrosine kinase inhibitor (TKI) therapy can control the disease for years, perhaps indefinitely in many patients. For other cancers, however, the success of kinase inhibition has been more modest. Despite great strides in drug design and delivery, resistance invariably develops, typically limiting median progression free survival (PFS) to a period of months. Development of new-generation inhibitors therefore has focused on increasing potency, overcoming resistance-conferring mutations to the drug target, and hitting parallel signaling pathways that bypass the target altogether. While sequential treatments and/or combination cocktails to circumvent resistance may work in some cases, concerns arise regarding toxicity and cost, prompting exploration of innovative new strategies to prolong PFS. Two recent studies in different cancers propose an alternative with a potential to increase the duration of tumor control by several already approved TKIs.
关键词：oncogene; overdose; ALK; BRAF; cancer ; therapeutics
