Cancer is a group of disorders stemming from abnormal cell growth in the body. The overall prevalence of cancer varies widely across the globe but will affect roughly 1 in 3 people in the United States alone. In many cases, cancer can be successfully treated through a combination of medical intervention and lifestyle adjustments. However, individual prognoses will differ based on the cancer type, how advanced the disease is, as well as unique genetic profiles of cancerous cells and the affected individual. Hence there is a continuing need to research more precise and effective therapies.
Monoclonal antibody for detection of sphingosine 1-phosphate (S1P) by immunostaining.
Potent, reversible inhibitor of lysoPLD activity of Autotaxin.
Recombinant human SHIP2, a lipid phosphatase acting on PIP3.
In the simplest terms, cancer is a disease of unchecked cell growth in the body. Under normal conditions cells divide via mitosis and when they become damaged or initiate cell death they are cleared and replaced with healthy cells. Abnormal cell growth can occur when the genes and proteins that regulate these processes accumulate too many mutations which frequently results in tumor formation, a hallmark of cancer.
Cancerous cells can diverge from normal cells in numerous ways, including: resistance to the immune system, growth in the absence of trophic factors, and aberrant angiogenic signaling. The last of these is notable as access to blood vessels is one of the mechanisms by which cancerous cells can spread or metastasize.
As with many diseases, genetics and mutations are some of the primary driving factors in cancer. Many mutations appear as single or point mutations in DNA that cause malfunctioning proteins to be produced. Other mutations can arise when double stranded breaks in DNA occur and are not repaired properly. Another form commonly seen in cancer is gene duplication, where partial or full chromosomes are not separated properly during mitosis.
In many cases, these mutations would be deleterious to the cell and it would be cleared via programmed cell death. However, when these mutations occur in specific sites or genes called tumor suppressor genes and oncogenes, they can lead to tumor development.
Any single mutation is typically insufficient to cause cancer, and cancerous mutations are predominantly acquired throughout one’s lifetime, though some cancers are hereditary. Tumor development and cancer usually arises via the accumulation of multiple mutations over time. This is why age and repeated exposure to specific agents or substances, carcinogens, are primary risk factors.
Outside of a clinical setting, cancer is sometimes spoken of as a single disorder that can appear anywhere in the body. But the reality is much more complicated. Globally, there are some genes that are more frequently mutated in cancer as a whole, such as those shown in the graph on the right. TP53 which encodes the p53 protein, is perhaps the most famous tumor suppressor gene and has been dubbed ‘the guardian of the genome’ for its protective functions. Similarly, PI3KCA is frequently mutated in cancer patients and is an ongoing target for therapeutic development with PI3K inhibitors showing promise both laboratory experiments or clinical trials.
Other genes with high mutation frequencies may appear low in overall but are enriched in specific cancer types. A classic example of this are the BRCA genes which contain mutations in approximately 50% of breast cancers but represent 5% or less of the total proportion of mutations. Additionally, as mentioned above, it is rare that cancerous samples contain single mutations and multiple genes are usually found to contain mutations.
Certain sets or groups of mutated genes also frequently appear together in specific cancer types and efforts such as the Cancer Genome Atlas Project have begun to outline how this may impact therapeutic development. This ‘mutational landscape‘ underscores the idea that treatment regimens can be tailored to address the needs of individual patients.