Re: PCI-32765 and CAL-101

[Guest guest]

At 10:20 AM 6/4/2011, S wrote:

> What would happen if one combined PCI-32765 with CAL-101?

Theoretically, since the two agents target two different

biochemical pathways, the combination of the two agents may

have advantages from an efficacy perspective.

For example, if a patient had clones of CLL cells in which

mutations existed that allowed one of the two pathways to be

bypassed by an alternative pathway, treating only with the

agent that targets the pathway with a mutated alternative

might not kill those mutated cells, whereas, the combination

of the two drugs would still kill the mutated clones because

the second agent kills the mutated clones by a different

mechanism, so it would not matter that the other pathway is

bypassed by an alternative pathway.

I expect the academic researchers who have both agents in

their possession have been tempted to do at least some in

vitro CLL cell experiments, involving comparisons of each

agent alone with both agents combined, using different

concentrations of each agent, to see whether synergy exists

when the agents are combined. However, most research

contracts between companies & academics place restrictions

on unauthorized use of " research materials " provided by the

companies. I have been on both the company and the

researcher sides of such contracts, understanding both the

research temptation and the need for a company to control

what is done with its intellectual property, especially when

it involves comparisons with drugs that may someday be the

market competition. Nevertheless, I would not be surprised

if some such 'unreported' comparisons have already been

performed.

Al Janski

[Guest guest]

I have the same thoughts, Al. What if we call the

biochemical pathways " light switches " .......It seems likely

that CLL has many " alternate light switches " that can be

turned on or off by different inhibitors. CLL is an

intelligent cancer with the ability to become refractory to

chemo and monoclonal antibodies. Such a smart cancer would

surely be similar to a maze. I think there is a " Master

Switch " that is like the Queen Bee. Hiding under all the

alternate switches, still wreaking havoc with it's

immortality------if this wasn't true, then we would not have

so many different treatments for seperate pathways. All

Roads Lead to Rome---finally, one of the pathways will

uncover the Queen. (that's just my view of CLL)

Jlou

Al wrote:

/message/15251

[Guest guest]

I can help with nomenclatura. Call them " CAL " and " PCI " .

CLL'ers will know what you're saying. Or CAL1 and PCI-

whatsamawhosit.

>

> What would happen if one combined PCI-32765 (when is this

> drug going to get an easy-to-remember name???) with CAL-101?

> Would that be too immunosuppressive? Would side effects be

> unmanageable? Would the FDA forbid it since neither drug is

> approved? Would it be super, super effective?

>