The mTOR's New Clothes

[Guest guest]

Here's a good overview of this and related treatment targets in cancer

cells.

Drug Development Spotlight: The mTOR's New Clothes?

http://lifesciencedigest.com/2010/11/22/drug-development-spotlight-the-mtor%

E2%80%99s-new-clothes

As discussed, CAL-101 is among the many promising drugs that target what are

hoped to be a critical pathways for the survival of malignant lymphoma

cells.

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Regarding PATHWAYS... here's a reworked explanation that might help the

blue-collar guys and gals among us to feel more at home with the term:

In the research papers we see references to drugs that target PATHWAYS in

cancer cells, which can be intimidating because of the cryptic names given

to these unfamiliar functions within the cells, such as PI3K / Akt / mTOR.

Relating cell biology to automobile systems (drive train, exhaust,

electrical, fuel) might help to demystify . at least it does for me.

Consider that the mechanic's job is to diagnose the problem - usually by

first isolating it to the system most likely to be causing the bad behavior,

such as: is there a spark? If no spark is seen, the problem is in the

electrical " pathway. "

And which part in the identified system? The fuel pathway has a storage

tank, fuel lines, filters, pumps, vacuum hoses, and a carburetor - where air

and fuel are mixed and then injected into the cylinder where the combustion

occurs (where the spark meets the fuel) where one system or pathway meets

the other.

So in the jargon of cellular biology, the fuel tank is " upstream of " (comes

before) the fuel line, which is upstream of the carburetor and the cylinder

where the combustion occurs, and the exhaust system where the key event

occurs (clearing the chamber) and so on.

Similarly, we might read in a cancer research paper: " Upstream signaling

inhibition enhances rapamycin [the drug] effect on growth of cancer cells "

to mean: a narrowing or blockage in the fuel line (upstream of the

carburetor) caused the engine to run slower or stop.

So while human cells are many times more complex than the familiar

combustion engine, there are some conceptual similarities - sufficient to

give us a feel for the biology of abnormal cells and what the researchers

are talking about.

You don't have to be a mechanic to effectively drive a car, but it can help

when you have a serious problem to have a feel for the subject - as in: does

this mechanic's proposed remedy seem plausible?

And you don't need to be an mechanic - or even familiar with the terms, to

know if the theory worked ... your car runs better or it doesn't; the

treatment with the targeted drug provides clinical benefit, or it doesn't,

when tested in a trial. " Mechanism is not evidence " even if proposed by

the greatest mechanic.

So when you read about a drug that targets the XYZ pathway, keep in mind

that it's just a name (made up by somebody) for a system within a cell -

which " drives " the bad behavior of the cell - such as rapid cell division

and a refusal to shut down and die.

BTW: chemo agents are also targeted drugs, because they act primarily on the

fast running cells (vehicles), but, yes, chemo upends the cop cars and fire

engines too. Fortunately, a new supply of these good cells can be reproduced

by our stem cells, which are not significantly affected by standard uses of

this intervention.

So chemo is also selective to a degree, and can be VERY effective against

lymphoma, but it's not as selective and specific to the problem as we hope

and expect therapy will be in the near future - a hope that is already

realized for some cancers, such as CML, which is effectively cured by a

single targeted agent.

So, we might fairly substitute the term " Automobile System " for " Cell

Pathway " to feel more comfortable when reading about and considering future

cancer therapies. But for those of us intimidated also by mechanical

systems, I do get that we will have to come up with another analogy. : )