Thursday, May 12, 2011

The biology of cancer treatment (part 3 of 3)

And finally, but very importantly, DNA repair...

DNA Repair
All four of the cell functions are broken in cancer cells because DNA mutations either inactivate or hyperactivate proteins that are central to those processes. The fifth and last process that gets broken in cancer cells is DNA repair itself.

Normal healthy cells regularly repair DNA damage (mutations) that occurs frequently in the cell. But when a mutation actually damages a gene required for repairing other mutations, then the total number of "unfixed" mutations in a cell can skyrocket. And so does the chance that a mutation will occur in a gene that produces a protein critical in one of the key four cell functions.

An analogy might be crime increasing when policemen themselves "go bad."

Relating all this to treatments
This mini biology lesson is highly relevant to treatment options -- current options as well as new ones in clinical development. Here is a quick, partial list of some common breast cancer treatment options and how they relate to the five cell processes we've discussed.

Herceptin (Cell growth control): HER2 is a cell surface receptor that sends a "grow" signal into the cell. In some breast cancers, there is an overabundance of HER2 molecules on the cell surface. This increases the signal. Herceptin binds to HER2, inhibiting it from sending the "grow" command and thus slowing tumor cell growth.

Tamoxifen and aromatase inhibitors (Cell growth control): Many breast cancers are fueled by estrogen, which binds to the estrogen receptor inside the cell to send a "grow" command (cells get multiple different grow commands, not just one). Tamoxifen works very differently than aromatase inhibitors (Arimidex, Femara and Aromasin) but the effect is the same: to damp down the estrogen-related grow signal.

Oncotype DX (Cell growth control, cell suicide, cell mobility). Measure the expression of 16 genes that are"turned on" at different levels in in in less aggressive vs. more aggressive tumors. Not surprisingly, the genes the test looks at relate to cell growth control (6 relate specifically to estrogen and HER2 signaling), mobility (also called "invasion", 2 genes), and proliferation (5 genes). Proliferation likely involves a combination of uncontrolled growth and the absence of normal cell suicide.

Avastin (Blood vessel formation). Avastin attaches to and inhibits a key protein involved in blood vessel formation called vascular endothelial growth factor (VEGF). Avastin are a treatment for breast cancer is controversial right now, but enormous research effort ihas and is being expended to target blood vessel formation using Avastin and other drugs.

BRCA testing (DNA repair): BRCA1 and 2 have multiple functions, but they are above all key players in repairing DNA damage. Inheriting one "broken" copy (one of the two you have on both of your parental chromosomes) of a gene that repairs DNA damage puts your cells at a disadvantage with regard to repairing cancer causing mutations. Thus the chance of getting cancer is increased.

We've just touched on these treatment options here, but in the coming weeks we'll be looking at these and other treatment options in more detail. Understanding a bit about the biology explains how newer treatment options work and why they are so exciting.

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