Axl is a receptor tyrosine kinase that is highly upregulated in cancer cells. Your PI is interested in generating a new therapeu
tic against this receptor, turning it into a start-up idea, and making millions off of the potential product. They want you to spearhead this product, and you (unwillingly) decide to go along with the plan. a. Your PI wants you to come up with a couple of different mechanisms on how to inhibit Axl. Propose one of those methods to target the drug specifically to cancer cells.
b. After trying to find DNA probes to target AXL tumors, you then have a realization that it's impossible. What makes cancer more difficult to diagnose with DNA probes than mendelian diseases (i.e., cystic fibrosis, sickle cell anemia, etc.)?
a. Overexpression of Axl receptor tyroxine kinase correlates with the decresed patient's overall survival and hence it's inhibition is under process.
AXL TKI BMS777607 treatment increased AXL protein levels after 24 h as observed by Western blot and flow cytometry analysis. Mechanistically, this inhibition-induced AXL cell surface accumulation was neither associated with epigenetic modifications, nor altered transcriptional and translational regulation. Hence this later increased the glycosylated protien abundance in kinase dead mutant. The kinase function blockaging resulted in impaired internalisation which finally incresed the level of proliferation.
An alternative technique may exist in linkage of Axl Tkl to a degradation machinery recruitment unit .
b. Mendelian disorders like cystic fibrosis results from error in the given DNA sequence which can be autosomal dominant and recessive both and also X or Y linked. Mutated gene results in the Mendelian disorders. Whereas in cancer there can be mutation or proliferation of the given cells in a specific area. In cancer cells there is 2.5 times more the mRNA present while 6.2times the DNA and hence the detection and diagnosis automatically becomes difficult as in Mendelian disorders only single sequence needs to be studied at a time .
Muscles act on joints antagonistically. Some muscles will contract while other contract pulling on bones around joint hence enabling movement. An example is the elbow joint is moved by antagonistic action of biceps and triceps. When your biceps contract and triceps relax you are able to bend your arm at your elbow. When your triceps contract and biceps relax, your arms straighten.
