Health & Medicine news on CML

November 6, 2008

June 25, 2008 - 02:56 in Health & Medicine " Activation of LYN kinase is

associated with resistance to imatinib (Gleevec) in patients with chronic

myelogenous leukemia (CML), researchers report in the June 24 online issue of

the Journal of the National Cancer Institute. Imatinib is the standard therapy

for newly diagnosed CML patients. However, some patients develop resistance to

the drug over time. In some patients, resistance develops in response to

mutations in the BCR-ABL gene. In other cases, though, researchers find no

mutations to explain the resistance. Previous work by Donato, Ph.D., of

the University of Michigan Comprehensive Cancer Center in Ann Arbor and others

suggested that one possible mechanism of this mutation-negative resistance is

the activation of LYN kinase, which is normally controlled by BCR-ABL in CML

cells.

" In an accompanying editorial, Deininger, M.D., Ph.D., of the Oregon

Health and Science University Cancer Institute in Portland and colleagues note

that the use of primary patient samples in the current study is particularly

important and provides clues as to how consistent LYN activation may occur in

CML. Further elucidation of this pathway will be essential, as will surveying a

larger patient sample to determine how frequently this type of resistance

develops in CML patients. "

Thursday, October 23, 2008 - 12:15 in Health & Medicine " Geneva, Switzerland:

Preliminary trials of a new multi-kinase inhibitor have indicated it has

impressive tumour shrinkage activity in patients with a difficult to treat type

of thyroid cancer. The results have put the drug's development on a fast track,

prompting the accelerated initiation of a large phase III trial. The compound,

XL184, targets cell growth and migration, as well as blood vessel growth

(angiogenesis), through inhibition of MET kinase, VEGFR and RET kinase.

" 84 patients with a variety of advanced tumours that were not amenable to

standard therapy were administered XL184 for either the first five days of a

14-day cycle or daily throughout the cycle. the percentage of patients with

either a partial response to the drug or prolonged stable disease for more than

three months - was 84% in the 25 patients who have been followed for at least

three months, said the study's presenter, Professor Sherman, chair of the

Department of Endocrine Neoplasia and Hormonal Disorders at M.D. Cancer

Center. Of the 84 patients, including patients with diverse cancers, disease

stabilisation for at least three months was seen in 28 cases. In sixteen of

those cases, the disease was stable for six months or more, the study found. The

most common adverse effects of the drug included diarrhoea (24%), nausea (18%)

and fatigue (15%). "

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