Drug Resistance!

Blog Post #1:

Cancer Degrading Drug!!!

Primary Article:

Sambol, E. et. al (2006). Flavopiridol Targets c-KIT Transcription and Induces Apoptosis in Gastrointestinal Stromal Tumor Cells. Cancer Research, Vol.66, pp. 5858-5866.

Blog Post #2:

Drug Resistant Lung Cancer
Posted by christina

Primary article:

Science (May18, 2007) Vol.316.no.5827,pp1039-1043

Summary:

Blog post #1 “Drug Resistant Lung Cancer” and Blog Post #2 “Cancer Degrading Drug” both discuss how the amplification of specific genes can result in drug resistance to tyrosine kinase inhibitors that are usually effective in the treatment of cancer. It is important to note that the tyrosine kinase inhibitors discussed in both of these articles are pharmaceutical agents/drugs not the natural tyrosine kinase inhibitors that are naturally present in the body. The genes and pathways discussed as well as the type of cancer being researched, however, are different in both articles.

The post entitled “Cancer Degrading Drug”, portrays how a mutation in cKIT, results in KIT amplification, and the resistance of GIST cells to the tyrosine kinase inhibitor known as imatinib mesyrate. Imatinib mesyrate normally regulates cellular development and functioning by preventing mutated forms of KIT from binding to bcr-abl receptors. Cellular resistance to imatinib mesyrate leads to increased cellular proliferation of GIST cells via continuous binding and transduction of cellular signals that activate GIST growth and division.

The post entitled “Drug resistant lung cancer”, states how a cellular mutation, results in MET amplification, and the resistance of epidermal growth factor receptors to gefitinib a type of tyrosine kinase inhibitor. Gefitinib normally functions to regulate the growth and proliferation of epidermal cells. Cellular resistance to gefitinib leads to increased cell proliferation of epidermal cells via continuous signaling of ERBB3.

The information found in these articles reinforces the idea we have frequently discussed in class, which is that cancer is the accumulation of several mutations that results in unregulated, uncontrolled cell proliferation. One of these mutations could result in gene amplification that results in cellular resistance to a specific tyrosine kinase inhibitor; current cancer drugs. The research presented within these articles, however, could pave the way to new, more effective cancer drug therapies.

Questions:

How do drugs function as tyrosine kinase inhibitors?

Is cellular resistance of specific tyrosine kinase inhibitors common in cancer?