From the suggested paper that I read (Therapeutic Advances in Medical Oncology, Shawna Leslie Organ, Ming-Sound Tsao 2011 "An overview of the c-Met Signalling pathway):
It confirms the RAF, MAPK connections.
"Interestingly, recent research has shown that non-small cell lung carcinomas with acquired resistance to EGFR inhibitors tend to show amplifications in MET [Bean et al, 2007; Engelman et al. 2007]. This suggests that combined treatment with EGFR and c-Met inhibitors could be necessary in a subset of patients to circumvent the onset of resistance to these drugs.”
Other interesting points
Activation of c-MET is a secondary event in various types of tumors, exacerbating the malignant properties of already transformed cells.
Events such as Hypoxia caused by the lack of oxygen diffusion to the centre of the growing tumor, is one mechanism that has been demonstrated to activate c-MET transcription in vitro and in vivo.
Ending in a "P" means "phosphate".
Ending in a "PP" means phosphate phosphatase" meaning it will remove the phosphate added by the Kinase.
I'm a chemist, not a biologist and I've been reading up on specific biology unrelated to oncology recently but in my birdeye's view:
If you see something end in an "R" (EGFR), it means "Receptor". If you see something end in a "K", it usually means "Kinase" which often means it will phosphorylate something.
In this case EGFR is a transmembrane receptor which puts it at the top of the metabolic cycle. There are a range of receptors and they cross pollinate to some extent. I view them as a spectrum where each one is slightly stronger in a more specific way than the other. It will affect many downstream processes but makes it a very general target and it will not 100% shut down very many processes it affects due to the cross pollination.
A receptor as a target will be better for general treatment but may not be the most effective but you may be able to use it more broadly.
By targeting a Kinase, you're getting closer and more specific to a process or specific disfunction whether it's activating transcription or another kinase.
Thus downregulating the activation of the EGFR receptor, you're also potentially down regulating many kinases as a result. Such as MAPK.
cMEt is also a receptor that also leads to MAPK.
If you've not already, perhaps check out acticle PMC3225017 at NCBI. Search "PMC3225017 NCBI" to find "An overview of the c-MET signaling pathway".
It looks informative on the biology. I'm about to read it. If you want to learn the biology, try not to limit yourself to the articles specifically about oncology drugs since the focus will be more on the drug than the biology.
MAPK does comes after MEK in the EG recetptor (EGFR) pathyway.
An additional note is that STAT3 is implicated in satellite cell recruitment as STAT3 is activated and activation of STAT3 in the area of a tumor would be and is bad.
Seeing how MEK precedes ERK in the relevant metabolism cycle, this seems redundant in some ways. The VEGFR2 lies upstream in the metabolism cycle (MEK, ERK) and has the advantage of possibly down regulating satellite cell recruitment. Blocking only VEGFR has the possible downside of other receptors co-regulating MEK and ERK which there are.
Shutting down too much might kill the host but there may be benefit from targeting other receptors that help regulate cell function. The biggest caveat that comes to my mind is that you may lose some specific cell type selection leading to more problems than solutions.
yahoo stats as of May 30th. Dividing the actual numbers, it does come out to 28%. Checking wsj, it's 25.6%.
I'm at a loss to explain Yahoos calculations. :P I'll change my response to 25.6%...
How's AMGEN treating you now " that the FDA has granted Breakthrough Therapy Designation to its experimental oncology drug, blinatumomab for the treatment of adults suffering from Philadelphia-negative (Ph-) relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL)."
This undermines Iclusig.
I hope that you understand that FDA approvals are based on current therapies which means that AMGEN's therapy undermines ARIA's Iclusig.
Good luck. Well, luck is no longer a factor for Aria. The bottom of your bag just broke. I hope you shorted ARIA.
Good news would make a spectacular short squeeze at 51% of float as short.
Ironically, I'd say that's about the same ratio for good news vs. bad news given what I know. I'm betting on good news.
Now the question, would you sell after a short squeeze in order to buy in a couple weeks after the dust settles?
Funny how you disappeared when they issued the convertible senior notes that puts the common shares out in the cold and the price dropped back to where it had been before the quick climb your were here bragging about.
I hope they have a lot of infrastructure built with common share money to pay back the senior notes before the commoners are stiffed.
What is your measure exactly? It's in the company's best interest to tightly control the enrollment process to ensure quality data from the trial.
Randomly giving drug to potential patients would be irresponsible and potentially damaging to a quality trial if there was adverse event for any reason related or unrelated to the dosing.
If a person qualifies for the study, there are avenues of funding available.
In fact, if you're concerned about a patient population, you should donate to a cause that helps fund care for the indication that concerns you. You will be helping someone that needs help. Beyond helping someone, the money will be helping fund new drug development and help drive the advancement of science in that area.
I think you mistook my intended meaning about gefitinib but it's not important. I did not express myself well.
FYI, it's eprint ATM. Once they do the physical publication, it's likely you can download it free from the ncbi-nlm-nih-gov site for free.
The question is if the biomarkers were of any use for predicting survival or increase in time of life with statistical significance.
Without reading it, I'd suspect that it only mentions cabo because the concept around cabo is based on a flurry of literature after gefitinib that pointed at two markers instead of one.
It might be an interesting article because determining where to look is a difficult problem. You can dose a drug and see a down stream affect but you may not know where you're target is. It could be one step away or 5 steps removed from where you see the change. Looking at the biomarkers and determining where you should be affecting it and where you are not is only one piece of the design.
My other question is if Timothy L Fitzgerald is related to Edward M. Fitzgerald of Ariad?
I think you mean default swaps and it's not the same as "shorting" the stock. It's removing all liability from them so they only make money. Guaranteed money is better than risky big money.