Why Treating Cancer is So Difficult, Part 1: Your Tumor is Not a Clone

There are many reasons, both scientific and clinical, that cancer is difficult to treat. I am going to dedicate a few posts to discussing this, so today is the first post in this series,

Part 1 // Your Tumor is Not a Clone

1997 was a big year for the word “clone.” It was the year we welcomed Dolly the sheep, the first mammal to be cloned from an adult cell. It was also the year that the movie Multiplicity with Michael Keaton came out. (Hi Steve!)

In cell biology, clones are identical cells that came from a single cell. In other words, one single cell started dividing. When the cell divides, it passes down its genetic information to the two new cells, so they are genetically identical. They are clones. If these two cells continue to divide, and divide, and divide, then you have a large number of clones that all came from that first parent cell.

Cancer is not clonal. Cancer is complex and heterogeneous (meaning that it’s not the same from one place in the tumor to another). There are also other types of cells other than cancer cells inside of a tumor: there are immune cells, there is extracellular matrix (the cellular “skeleton” to help anchor the tumor and give it shape), and many others inside what is called the tumor microenvironment. Other than the complex tumor microenvironment, there are often differences in the cancer cells in a single tumor.

As a tumor forms and grows, cancer cells continue to grow and divide in a way that normal, non-cancer cells cannot. This is one of the ways that cancer cells are distinct from other cells in your body — they have limitless potential to survive and divide. One way this happens is by the cancer cells acquiring mutations in certain genes that allow them to ignore those normal signals a cell receives to stop dividing.

Since a tumor can continue to acquire gene mutations over time, it is possible that not every cell in a tumor has the same mutations. When a patient goes to a clinic to get a biopsy, often only one part of the tumor is examined. A program for cancer therapy will be prescribed based on this information, for example chemotherapy. However, if there are some parts of the tumor that could be resistant to the prescribed therapy, there are some questions to consider.

What is the effect be of the medication on the tumor as a whole if these sub-clones exist?

Will a therapy that only has an effect on one part of the tumor lead to another part of the tumor becoming more resistant to therapy, and therefore difficult to treat later?

Could treatment of only a part of the tumor (or rather, if only one part of the tumor responds to a therapy) contribute to increased tumor progression or metastasis?

Is it possible to biopsy and examine multiple parts of a tumor, and then combine therapies based on a patient’s unique and varied tumor characteristics?

These are great questions that researchers are seeking to answer. Now that sequencing (looking at the genetic code of a tissue) is becoming more commonplace in cancer treatment, patients and doctors can move closer to the idea of personalized medicine.

// Want to learn more?

Why don’t we have a cure for cancer? Check out this podcast, starting around 22:40.

What is Precision Medicine and how is it helping people? Check out information from President Obama’s Personalized Medicine Initiative.

How are researchers tackling the issue of tumor heterogeneity? A conversation with Dr. Scott W. Lowe, head of the Geoffrey Beene Cancer Research Center at the Memorial Sloan Kettering Cancer Center in NYC.