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media
Unlike other human therapeutic monoclonal antibodies, which can target only proteins that remain on the outside of cancer cells, the new monoclonal antibody, called ESK1, targets a protein that resides on the inside of the cell.
ESK1 is directed at a protein called WT1, which is overexpressed in a range of leukemias and other cancers including myeloma and breast, ovarian, and colorectal cancers. WT1 is a high priority target for cancer drugs because it is an oncogenic protein, meaning that it supports the formation of cancer. In addition, it is found in few healthy cells, so there are less likely to be side effects from drugs that target it.
"This is a new approach for attacking WT1, an important cancer target, with an antibody therapy. This is something that was previously not possible," said David A. Scheinberg, MD, PhD, Chair of the Sloan-Kettering Institute's Molecular Pharmacology and Chemistry Program and an inventor of the antibody. "There has not been a way to make small molecule drugs that can inhibit WT1 function. Our research shows that you can use a monoclonal antibody to recognize a cancer-associated protein inside a cell, and it will destroy the cell."
The first studies of the antibody are showing promise in preclinical research as a treatment for leukemia as reported March 13, 2013, in Science Translational Medicine. .........
Will the monoclonal antibody ever reach inside the "individual" cancer cell?
ReplyDeleteIt may be very important to zero in on different proteins. However, when actually taking the "targeted" drug, will it even enter the cancer cell? Once entered, does it immediately get metabolized or pumped out, or does it accumulate? In other words, will it work for every individual patient that tested positive for the target?
Simply having a target (even inside the cell) doesn't ensure that the drug will work. The drug might not get inside the cell at all. The drug can get pumped out of the cell. The drug can be inactivated by the cell. The cell can recover from the damage called by the drug by repairing damage or shutting down the cell death pathway or whatever.
All the validations of this protein or that protein provides us with a variety of sophisticated techniques to provide new insights into the tumorigenic process, but if the "targeted" drug either won't "get in" in the first place or if it gets pumped out/extruded or if it gets immediately metabolized inside the cell, it just isn't going to work.
Metabolism is the principal driver of human cancer. Cells speak to each other and the messages they send are interpreted via intracellular and intercellular pathways. You wouldn't know this using analyte-based proteomic methodologies. However, functional phenotype analysis can provide the window by testing various cell-death signaling pathways upstream and downstream.