Several hundred thousand labs in universities and companies are looking at cancer from every angle to find new ways to eliminate it. While there are many aspects of cancer biology being explored, much of the current research for potential new treatments focuses on several distinct aspects and unique traits of cancer cell biology.
Fixing Signaling Pathways That Control Cell Growth
Uncontrolled growth and replication is the main difference between cancer cells and normal cells. In normal cells, growth and replication is one of the processes controlled by a very complicated network of proteins that communicate information in the cell from sensors on the surface of the cell (i.e., receptors). This communication is done by passing chemical changes sequentially down a cascade from one protein to the next so the cell makes changes to internal reactions in response, for example it may activate certain genes, start cell division, or make more of certain proteins. One of the main proteins in these networks are kinases which transmit signals by adding phosphates onto the next protein in the cascade. Cancer cells have mutated genes in these signaling pathways to "lock on" signals for continual growth and replication. A major focus of cancer research for more than a couple decades has been to understand these pathways better by understanding how particular cancers disrupt the normal signaling and identifying the kinases and other proteins in the pathway that can be targeted with drugs to turn off the locked replication signal. A number of kinase inhibitor drugs have been developed and a majority of cancer drug research continues to focus on these type of targets. Companies such as ArQule, ACTBiotech, Exelexis, and Kinex and recent start-up Blueprint Medicine focus drug development efforts on targeting cancer aberrations in these signaling pathways.
Targeting Non-Coding RNA that Regulates Gene Expression
Ribonucleic acid (RNA) is usually produced in long strands that carry the DNA code specifying a protein to the part of the cells where proteins are made. In the late-1990s, though, it was found that some small RNA molecules had another function where they directly interfered with making proteins. Since the discovery of these small interfering RNA, other types of RNA have been found that regulate DNA and gene processing rather than being used to just make proteins. Recent research has found that there are changes to a number of these RNA molecules with regulatory functions in cancer cells and they may be required for cancer cells to override normal growth controls. Focused research in this area for potential targets for cancer treatment is really just starting but abnormal non-coding RNA has been implicated in several cancers, for example breast cancer metastasis and prostate tumor growth suggest this avenue of investigation seems to have significant therapeutic potential.
Turning On Epigenetic Controls That Keep Genes Off
Every human body cell has all human genes, but only a small portion of them are actually used in any particular cell. Only some genes are needed for liver cells to function, and some other genes to for skin cells to do what they do, etc. Normal cells more or less permanently shut off most of their genes by making small chemical changes to the DNA and, when they replicate, the patterns of genes that are shut off is passed on to progeny cells. These epigenetic changes are yet another way cells regulate themselves to play their assigned role in the body, and so they are another target cancer cells disrupt when gaining the ability grow and replicate uncontrollably. Not only does cancer change DNA with mutations, but it alters large regions of DNA that are not normally expressed. Several drugs have been approved that affect epigenetic regulation, and more are in trials.
Slowing Down Metabolism by Cutting Off the Supply of Glucose
Glucose is the main form of sugar the body uses to generate energy, and cancer cell require excessive amounts of glucose to fuel growth and development. This particular trait was just added as a hallmark of cancer although it is has been a known trait of cancer cells for over 80 years. Much of the early biochemical research focused on how cells use sugar to make energy, so much so that, at this point, this process is a core part basic high school biology classes and was uninteresting to many researchers looking to more interesting areas of investigation. However, it has recently become clear that many of the mutations in cancer cells seem to have a direct role in increasing the rate of metabolism. Recent studies published in Nature, discoveries by researchers at Johns Hopkins, and screening results from companies such as Cornerstone Pharmaceuticals and Agios indicate this may be a fruitful approach for future therapeutics.
Triggering An Immune Response to Kill Cancer Cells
Although cancer cells are derived from normal body cells, they are very abnormal, and should trigger an immune response to kill and dispose of them. In fact, cancer cells are usually seen by the immune system early in their development and eliminated before they have chance to develop further. You can actually watch a video of a immune-killer T-cell attacking a cancer cell in this video. This means that cancer cells that manage to advance to malignancy can somehow evade immune system detection. Since many aspects of both the immune system and cancer pathology are still not well understood, there is a lot unknown about how various cancers accomplish this evasion. However, getting the body's own immune system to recognize a cancer could be a powerful treatment approach. After many years of work on this approach, there finally seems to be some progress towards targeted cancer vaccines that would get the immune system to recognize and destroy cancer cells.
Activating the Programmed Cell Death Response (Apoptosis)
A serious abnormality in normal cells triggers a "cell suicide" program called apoptosis in virtually all types of cells. Noted as one of the hallmarks of cancer, malignant cells have to suppress this response to survive. Research in how cancer cells manage this suppression has been ongoing with the thinking that drugs might be developed to either force an apoptosis response to kill the cells, or reverse the cancer cell's ability to suppress its own normal response. The last several years have produced a much more detailed understanding of the genes cancer cells alter to suppress the apoptotic response, which makes it clearer what need to be targeted to get cancer cells to self destruct with this program.
Inhibiting Tumor Vascular Formation (Anti-Angiogenesis)
A very well-known characteristic in larger tumors is the presence of tubes and blood vessels. Cells in a tumor, just like in normal tissue, need to get nutrients and oxygen to survive so, for tumors to form and grow, they need blood flow like normal tissues. Since this tumor vascularizaion was first recognized over 100 years ago, researchers have long thought that preventing this vascular growth might inhibit tumor growth. However, until researchers at Genentech, in 1980, isolated vascular endothelial growth factor (VEGF), there wasn't a way to do it. Once this factor was found, Genentech went on to launch the first anti-angiogenic cancer drug Avastin, which was approved in 2004. Currently, there are a number of approved angiogensis inhibitors for cancer treatment and the search for new more effective ones continues.
