A Basic Science Perspective of the Challenges Facing Cancer Researchers

The Issue

 Cancer is a disease that has touched the lives of millions of people around the world.  Despite billions of dollars in spending and countless research hours, a cure has yet to be developed.  For many, this concept may be difficult to fathom.  What is the delay?  Why have scientists not figured this out?  Although these are simple questions, the answers are not so straightforward.  A vast amount of literature is available on the diagnosis and physiological understanding of cancer.  However, this article will overview the less common, molecular field of cancer.  This perspective will shed some light on what the current challenges are and why progress appears slow.

Basic Overview of Cancer

Cancer can be defined as the deregulated growth of a cell.  Normally, cells grow for a certain amount of time and then die.  However, in the case of cancer, cell growth is continuous.  As the cancer cell growth continues, the group of cells creates an ‘island’ in the body and develops a novel supply of nutrients from the blood.  This process, angiogenesis, generates new blood vessels that provide the group of cancer cells with all the necessities to support further growth.  This cancer island is then protected from the body’s defence system and is free to continue growth without disruption.  However, this concept begs the question, how did the cells become deregulated in the first place? This question is best addressed through basic molecular biology.

Molecular Biology of Cancer

Proteins predominantly control the various biological functions of a cell (growth, death, differentiation etc).  The proteins themselves are subject to tight regulation to avoid adverse effects on a cell such as deregulated growth.  This protein regulation occurs in many forms such as timely/tissue specific expression of the protein from the gene that encodes for it, modifying the protein to turn it on and controlling binding to targets that allow the protein to function.  These different forms of regulation keep an active protein under control so that a task starts and stops exactly when/where required.  For example, if a cell needs to grow, a protein(s) will become activated in order to allow the growth process to occur.  However, if this protein becomes over active, the cells will continue to grow endlessly and a potential tumour will arise.  This illustrates the need for a tight regulation of protein activity. 

A simple overview of the molecular biology of cancer, divides proteins in two categories, oncogenes and tumour suppressors.  Proto-oncogenes naturally express proteins in the cell that promote growth, whereas tumour suppressor proteins inhibit this process.  If a proto-oncogene becomes overactive or overexpressed, it becomes an oncogene, which converts a normal cell to a cancer cell.  A proto-oncogene can become an oncogene in a few ways.  One possibility is that a proto-oncogene is mutated and either over-expresses the corresponding protein or alters a regulatory portion of the protein.  Another option is that the proto-oncogene expresses too much of a protein or the protein persists for too long.  A third possibility is through genetic mutation where a proto-oncogene is expressed in the wrong cells, at the wrong time or is merged with another protein and in turn, has enhanced activity.  Regardless, of the mechanism of converting a proto-oncogene to an oncogene, the outcome is an overactive protein and deregulated growth.  Another option for deregulated growth is the dysfunction of tumour suppressors.  Overall, a disruption in the balance between proto-oncogenic growth and tumour suppressor mediated inhibition can result in a deregulated cell and the transition from a normal cell to a cancer cell. 

With this basic overview of the molecular biology of cancer, the original questions of what is the delay? why have scientists not figured this out?  still remain.  The difficulty is that 1% of all human genes have a potential role is cancer, according to the Wellcome Trust Sanger Institute.  The exact number is always changing as new roles for proteins are constantly discovered.  The issue is further complicated as specific proteins promote cancer in only one cell types.  Since there are so many culprit proteins, a therapy targeting one or a few proteins may not be suitable for all forms of cancer.  Medical science research works on the principle of understanding the normal function, identifying the disease-causing change and then restoring the normal function.  With new roles for proteins in cancer constantly being discovered, it is rather difficult to develop a cure.  However, with endless determination, research continues to move forward.  The next article will focus on some of the new and more promising therapies, which are showing tremendous potential in clinical trials.