Tuesday, May 10, 2011

The biology of cancer treatment (Part 1 of 3)



One of our main goals at LATESTBreastCancer is to help patients understand the biology of cancer so that they can better understand current and potential treatments (for example, new kinds of gene-based tests, drugs in clinical trials, etc.). This week kicks that off.

To begin, we need a basic and common understanding of what cancer is and a language to describe it. With that framework (note 1), we'll be able to mentally place later blog entries about specific treatments into a larger perspective. In general, I don't want to focus on basic biology as a topic unto itself. Rather, I want to explain biology only to the extent it's needed to understand treatment.

We'll start by telling the whole story of cancer in one paragraph and then go into individual chapters over the next couple days.

The Whole Story (quick version)
Cancer is caused when mutations in the DNA (genes) inside breast cells cause proteins--proteins that normally perform important cell functions--to work improperly.

Problems with these proteins can be grouped into four categories based on the functions of the cell that they "break." All four of the following cell functions go awry as tumor cells progress toward dangerous metastatic behavior.

1) Cell growth control (this breaks)
2) Programmed cell suicide (this breaks)
3) Blood vessel formation (becomes abnormally active)
4) Cell mobility (becomes abnormally active)

There is one additional underlying cell function that breaks and makes the tumor cell more susceptible to the other four problems. It's DNA repair. When the cell's ability to repair DNA damage is itself damaged, then mutations that cause problems with the other four processes are more likely to occur.

Let's look at each of these four (really 5, including DNA repair) cell functions that break. At the end, we'll look at specific breast cancer treatments like Herceptin, Avastin and OncotypeDX and see how they fit into this story.

Cell growth control
The first cell function that breaks is the cell's ability to control its growth (note 2). Normal cells grow (proliferate) and divide only when signaling molecules from outside the cell attach to receptors on the cell's surface and send a growth signal through a series of proteins into the cell nucleus. In the nucleus, specific genes required for cell growth and division are turned on.

Cancer cells have broken signaling genes that send the "grow" signal into the cell's nucleus even though no signal was received from outside the cell. Think of this as "the foot being on the gas pedal all the time." Broken cell signaling is the first step (or at least a very early step) in a normal cell becoming a cancer cell.

Tomorrow: Steps 2, 3 and 4.

Note 1: To give credit where it's due, the framework I'll use is a slightly simplified version of one proposed by Hanahan and Weinberg (2000) that's commonly used in the field.

Note 2: Scientists don't know to what extent cell functions have to break in the order that I'll present. But many assume that they break roughly in this order.

2 comments:

  1. Remarkable post. Your post is a great help to understand how cancer actually grows in our body and the way when it is treated it stops from spreading more. I have understood all the three parts that you have explained and found all of them an excellent source to understand the biology of cancer.
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