[bedris]

This study details the use of a peptide-drug conjugate; these are drugs with peptides (small proteins) chemically conjugated to cytotoxic drugs.

The idea behind these conjugated drugs is that the peptide portion of the drug hones in on a specific biological target and the conjugated cytotoxic drug then kills the cells that have been recognized by the peptide (think warhead and payload). In this case, the peptide recognized prostate-specific membrane antigen, which is expressed on prostate cancer cells, and the cytotoxic drug was one derived from Thapsia garganica, the toxic weed (cytotoxic drugs being isolated from plants is nothing new, of course).

A more common class of these conjugated therapies are called antibody-drug conjugates[1], where an antibody molecule (instead of a peptide) is linked to a cytotoxic drug. There is currently one of these drugs, Brentuximab vedotin, FDA-approved for the treatment of cancer[2]. There are many more under preclinical or clinical development.

[1] http://en.wikipedia.org/wiki/Antibody-drug_conjugate [2] http://en.wikipedia.org/wiki/Brentuximab_vedotin

[presidentender]

So if prostate cancer has metastasized, and we target the cancer, do we do so at the hazard of exposing the healthy prostate cells to the same fate?

Do the cells of other cancer-prone organs produce similarly specific antigens?

If so, how do we avoid the situation where we eliminate (for instance) melanoma tumors of the brain and lungs only to have the patient's skin kill itself off completely?

[bedris]

I think that all of your questions come down to two core concepts: therapeutic index and antigen stability.

For therapeutic index, you want to identify and target antigens that show the largest difference between cancerous tissues and normal tissues (i.e., antigens with a large therapeutic index). In other words, you'd want your drug to bind to an antigen that's present at a higher level on the prostate cancer cells than the normal prostate cells, such that the normal cells are spared.

For antigen stability, you ideally want your drug to target an antigen whose expression is maintained in metastatic lesions. In other words, if a cancer metastasizes from a primary site to a distant organ, and the antigen your drug targets is maintained on the cancerous cells that have made their way to the distant site, then that is a more therapeutically amenable target then one whose expression is lost upon tumor metastasis.

Do those explanations answer your questions well? Let me know if you'd like me to clarify more.

[presidentender]

The theraputic index explanation cleared my questions right up. Thanks!