Thursday, August 7, 2014

It's Complicated - cancer that is.

Have you ever wondered why a cure for breast cancer once it has metastasized has not been found?

No, it is not the big pharmaceutical companies hiding cures from the public because it would affect their profits.

No, it is not some government conspiracy trying to keep population numbers down.

Actually . . .

It only takes a few minutes to read a scientific article about the signaling pathways inside a cancer cell to understand the reason there is no cure yet is . . . it's complicated—very, VERY complicated.

Take a look at the diagram below showing many of the signaling pathways within a cell.

On the outside of the cell are growth factors. These growth factor receptors sometimes are the beginning of a cancerous pathway. Inside the cell you will see PI3K and Akt. One fourth of breast cancers have a defect in the PI3K pathway. This pathway along with others begins with a gene that makes a protein. This protein activates a molecule. Other molecules are soon activated along a set course that when completed carries out a particular cellular function. PI3K is an enzyme (a special kind of protein) involved in the activation of the protein Akt. The Akt then activates mTOR which causes the cell to grow and proliferate. If mTOR mutates or its activation is controlled by other mechanisms within the cell. Then uncontrolled growth can occur. MTOR is very active in many types of cancers.

In normal cells there are PTENs that repair any mutations or damage to a cell that occurs. If the damage cannot be repaired, the cell experiences apoptosis-- cell death. Sometimes the PTENs are missing which of course is bad because damage to the cell cannot be repaired, nor does the cell die as it should. The cell is then able to make duplicates of itself with the defect and, you guessed it, a monster is on the loose.

I read recently that once a cancerous pathway is established, it travels in a continuous loop. There is no end to the pathway and the cellular function that is created unless something intercepts it. In normal cells, pathways have a halting mechanism to stop those cellular functions when no longer needed. But, in cancer cells, mutations in pathways can cause specific cellular functions to occur non-stop creating a very out of control machine that will replicate itself over and over pushing all the normal cells out of the way in a battle for space.

Amazing and terrifying, isn’t it?  

Below are two wonderful illustrations of pathways within a cell. After finding these pictures on the internet, I decided I had to share them, and the result is this post. 

If you look at the above picture you will see the HER 2 receptor on the outside of the cell. In my case, these receptors have become more numerous than normal. HER 2 neu over-expression can occur in the cells of other types of cancers as well.

When a ligand (a molecule, a hormone, drug or antibody) attaches to a receptor, it begins the signaling necessary for the pathway to be activated. My treatment involves Herceptin with a chemo drug attached--DM1. Herceptin attaches to a HER 2 receptor taking the place of a natural ligand. Once it attaches, the chemo drug is released directly to the cancer. TDM1 inhibits cell signaling through the PI3K/AKT pathway and promotes apoptosis (cell death). Super cool, right?

Because of cancer’s complexity, no two people have exactly the same cancer. There are differences in the genes that have mutated and differences in the pathways that a cancer uses for survival, growth and proliferation. That is why one type of cancer does not respond the same way a seemingly similar cancer does to a particular drug.

To complicated matters further, within one tumor there can be cells that have different mutations than their neighbor. Read this Medical News Today.

Yup, it’s complicated.

Cancer is also very good at surviving. When a pathway is interrupted by a drug, cancer cells find new branches in their pathways in order to continue their survival. It is believed that the cancer cells can even make their surrounding environment conducive to their survival and spread.

Today, a lot of cancer treatment is a guessing game.  A person is given a drug based on their cancer type and the results of clinical trials. Many drugs are given with little knowledge as to whether it will work or not. Currently, many of the chemotherapy drugs are not targeted to a specific protein. Instead, the drugs target fast dividing cells – healthy and cancerous. Since healthy cells are affected some very nasty side-effects can occur. Very often these drugs only affect a cell in a particular phase in its life. Those phases are growth, copying of the genes in the creation of a new cell (replication), and division. Depending on the phase a cell is in upon the arrival of a drug determines how effective it will be. Some cells may be in a resting phase and are not affected by many drugs. There are some drugs that can affect all phases, thankfully. Many times, several chemotherapy drugs are given together to try to affect more cells going through the different phases at any given moment.  

In the future, as more targeted therapies are developed, treatment should become more personalized. It will be wonderful when scientists can take a person’s cancer cells and determine which proteins in a particular pathway need to be targeted. Then a drug can be selected/developed and delivered to a particular receptor and halt one of the proteins in the pathway. Being able to target only the cancer cell and knowing which pathways to intercept will stop so much of the suffering associated with giving drugs that affect healthy cells too. Targeted therapies – like the one I am being treated with -- will allow people to have a better quality of life, and hopefully live longer.

The complicated cellular machine that makes up all of us is slowly being unraveled. My very brief and simplistic attempt at explaining why cancer is so difficult to cure I hope has left you with the realization that the cure for breast cancer will not happen in the near future. Just Google “Breast Cancer Pathways” and the enormity of what scientists are trying to uncover will be revealed.

I am not a cellular biologist, just a person who finds biology fascinating, so if any of my information is incorrect, please let me know by commenting below.

For more information on types of targeted therapies, see Understanding Targeted Therapies: An Overview at

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