[suzierose]

Keys to overcoming bortezomib & lenalidomide resistance

by suzierose on Fri Jan 20, 2012 4:56 pm

Blocking IGF-1 restores sensitivity to bortezomib

ASH Abstract 925

They found that the insulin-like growth factor (IGF-1) pathway is active in myeloma cell lines that are resistant to bortezomib. Knocking down the IGF-1 receptor with small hairpin RNA (shRNA) restored sensitivity to the drug.

Treating with the experimental IGF-1 receptor inhibitor OSI-906 alone killed bortezomib-resistant myeloma cells but had little effect against cells that had not been treated with bortezomib. Combining the two drugs increased myeloma cell death.

"So we have cell surface expression of the IGF1 receptor as a potential biomarker for treating bortezomib-refractory multiple myeloma with an IGF1 inhibitor," Orlowski says. Instructor Deborah Kuhn, Ph.D., presented this research at ASH.

Blocking Wnt/Beta-catenin pathway empowers lenalidomide

ASH Abstract 928

Orlowski's lab previously showed this pathway causes resistance to lenalidomide and implicated one pathway component in particular, the cell surface protein CD44.

Adding the drug all-trans-retinoic acid (ATRA), which is known to inactivate beta-catenin signaling, to lenalidomide treatment killed lenalidomide-resistant cells and reduced the presence of CD44 by up to 60%.

The team then combined lenalidomide with the experimental small-molecule drug FH535, which disrupts beta-catenin activity. The combination also increased cell death in resistant multiple myeloma cell lines.

They also found that lenalidomide treatment increases levels of CD44 and that knocking down CD44 with shRNA made lenalidomide-resistant cells vulnerable to lenalidomide.

An extensive analysis of gene expression data from myeloma samples at the Multiple Myeloma Research Consortium showed that high CD44 levels are significantly associated with poor prognosis.

CD44, therefore, is a potential biomarker for combining ATRA or another beta-catenin targeting drug with lenalidomide to overcome lenalidomide-resistant multiple myeloma. Post-doctoral fellow Chad Bjorklund, Ph.D., presented this research at ASH.

http://www2.mdanderson.org/cancerfrontline/2011/12/researchers-find-barriers-to-multiple-myeloma-drugs-and-keys-to-unlock-them.html

[Larry]

Re: Keys to overcoming bortezomib & lenalidomide resistance

by Larry on Mon Jan 23, 2012 1:38 pm

My father who is 90 years old begins treatment today for multiple myleoma. He lives in Tennessee and I am in Texas. I want to be as supportive as possible since I am 14 hours away. He is beginning with a steriod shot and Velcade. Can anyone tell me what side effects that were experienced in this type of therapy. Thank you so much!

[dsdhimanm]

Re: Keys to overcoming bortezomib & lenalidomide resistance

by dsdhimanm on Sun Jul 29, 2012 12:10 pm

My brother is suffering from multiple myeloma and now he has resistant to bortezomib now because m bands are increase. Or there is superious drug which we are taking . kindly tell alternative for him.