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susceptible to other drugs that function in a slightly different way.
Navy Seal Teams = Monoclonal Antibodies
Think about a trained platoon of Navy Seals whose mission is to kill foreign troops that have occupied a city. They are trained to recognize enemy soldiers by watching out for distinctive features of the enemy, such as their speaking a unique language. The highly trained Seals will initially do a good job of picking off the enemy troops and significantly reduce their numbers. However, the enemy soldiers will eventually spread the word among their remaining troops to stop speaking their native language. Their numbers will then increase because they can now evade your ability to identify and kill them. Unfortunately, there will also be some civilians who are not enemy soldiers who will be killed because, by chance, they happen to speak that same unique language. Despite the initial success of the Seals, they will need to change their strategies over time so that they can recognize the enemy by some other characteristic.
This analogy basically describes how monoclonal antibodies (e.g. rituximab (Rituxan)) kill off tumor cells. These antibodies recognize molecules on the cell surface that, in an ideal world, would only be found on cancer cells. Unfortunately, these same proteins are sometimes found on normal cells, and the antibodies attack them as well. Unlike chemotherapy, which is non-specifically toxic to both normal and cancer cells, the approach here is to focus the attack primarily on the cancer cells. These targeted antibodies won’t kill some cancer cells because they either don’t have the molecule that the antibody is looking for on their cell surface, or the cells have developed a resistance to the drug via some other mechanism. These surviving cancer cells may then replicate to regrow the tumor, which may (or may not) be susceptible to other drugs.
Smart Bombs = Antibody-Drug Conjugates
This approach is similar to the situation described above where the Seals are engaging an infiltrating army of enemy soldiers. In this situation, however, the Seals are much better armed: they carry hand grenades that they can use to kill the enemy. This makes them much more effective than their fellow fighters that lack these weapons. As before, enemy soldiers that can’t be recognized can’t be killed.
Antibody-drug conjugates (e.g. brentuximab vedotin (Adcetris)) use monoclonal antibodies to deliver a payload of highly toxic molecules to cells to which the antibody binds via a specific cell surface molecule. Two things are needed for this therapy to be effective: the targeted molecule should be found only (or mostly) on the cancer cells, and the toxic molecule should not be released until it is inside the targeted cell. These toxic molecules are so poisonous that … Next Page »