Researchers Identify Genetic Markers ...

Researchers Identify Genetic Markers That Predict Efficacy of Novel Cancer Drug

There are 2 comments on the Newswise story from May 30, 2008, titled Researchers Identify Genetic Markers That Predict Efficacy of Novel Cancer Drug. In it, Newswise reports that:

Researchers at the University of Southern California and USC/Norris Comprehensive Cancer Center have identified genetic markers in cancer cells that predicted the benefit of a novel cancer drug prior to ...

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Since: Dec 05

Irvington, NJ

#1 May 30, 2008
A monoclonal antibody is a "large" molecule. It attaches to specific proteins on the outside of cancer cells but does not have a convenient way to access a large majority of the targeted cells on the inside, which are protected from the drug.

There is also multicellular resistance, which means the drugs affecting only the cells on the outside may not kill these cells if they are in contact with cells on the inside. The cells may pass "small" molecules back and forth.

"Small" molecule inhibitors are enzymes that make biologic processes happen faster and are often key junctions in signaling pathways. It is a key intermediary in the EGF cascade pathway.

Vatalanib (PTK/ZK) is a "small" molecule tyrosine kinase inhibitor but with broad specificity that targets all VEGF receptors (VEGFR). It is a multi-VEGFR inhibitor which inhibits the activity of all known receptors that bind VEGF, VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1), and VEGFR-3 (Flt-4).

There are so many drugs out there! The needed change in the war on cancer will not be on the types of expensive drugs being developed, but on the understanding of all the drugs we already have. The system is overloaded with drugs and underloaded with the wisdom and expertise for using them.

Companion molecular diagnostics often have been mostly or totally ineffective at identifying clinical responders (durable and otherwise) to the various therapies.

If you find one or more implicated genes in a patientís tumor cells, how do you know if they are functional (is the encoded protein actually produced)? If the protein is produced, is it functional? If the protein is functional, how is it interacting with other functional proteins in the cell?

All cells exist in a state of dynamic tension in which several internal and external forces work with and against each other. Just detecting an amplified or deleted gene wonít tell you anything about protein interactions. Are you sure that youíve identified every single gene that might influence sensitivity or resistance to a certain class of drug?

Assuming you resolve all of the preceeding issues, youíll never be able to distinguish between susceptibility of the cell to different drugs in the same class. Nor can you tell anything about susceptibility to drug combinations. And what about external facts such as drug uptake into the cell? You're not going to accomplish this using a genetic marker.

The "cell" is a system, an integrated, interacting network of genes, proteins and other cellular constituents that produce functions. You need to analyze the systems' response to drug treatments, not just one or a few targets or pathways.
Mariano
#2 Sep 23, 2013
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