Science & Genomics
Learn here about how Basin Genomics is using genomics to develop a novel oral cancer screening.
How Cancer Forms
Cancer occurs when the DNA of normal cells is altered or damaged, resulting in uncontrollable growth of affected cells. Accumulation of these cancerous cells results in formation of a tumor. Typically, cells are programmed to prevent tumor formation through behaviors such as differentiation or self-destruction. Unfortunately, cells with damaged DNA may not be capable of performing these mechanisms, making it possible for cancer to develop.
There are many types of DNA abnormalities that can affect cell functioning, such as DNA mutations, deletions, amplifications, and rearrangements. These changes can cause cells to produce abnormal amounts of certain proteins or make proteins that do not function properly. Proteins have many important roles in the body, such as repairing tissues, catalyzing metabolic reactions, and providing structure to cells.
Often, the DNA of a cancer cell acquires a combination of several genetic alterations. Some of these genetic changes are inheritable, while others are caused by environmental factors (exposure to UV light, tobacco, etc.) or occur during normal processes like cell division. The changes that accumulate in a person’s genome over their lifetime are called somatic changes and account for 95% of all cancer cases. Therefore, understanding these changes is essential for creating successful cancer treatments.
Cancer genomics is a newer field that focuses on studying the differences in DNA sequences of cancer cells compared to normal cells. Specifically, cancer genomics looks at gene activity in cancer cell DNA to determine which proteins are abnormally active or silenced, a factor that can be responsible for the cells’ unregulated growth and ability to evade the body’s immune system.
The idea behind the study of cancer genomics is that, if we understand what genetic changes have occurred to cause a certain cancer, then treatments can be developed to combat the specific DNA errors that are responsible. These treatments would only target the genetic errors, unlike treatments such as radiation and chemotherapy that affect healthy cells and tissue along with cancerous cells.
HPV+ Head & Neck Cancer
For most people, the body’s immune system can fight off HPV naturally, and infected cells can return back to normal. However, in some cases, the body is not able to fight off the infection, and diseases like oropharyngeal cancer can arise. Cancer caused by HPV usually takes years to develop after initial infection. Currently, it is unclear if HPV alone is enough to cause oropharyngeal cancers, or if other factors (such as tobacco use) have to also be present to induce cancer. However, over the past 20 years, cases of OPC associated with HPV have increased in younger men and women without traditional risk factors, such as smoking and drinking.
HPV carries cancer-causing genes known as E6 and E7. When the virus integrates into the cell genome, causing errors in the new copies of DNA produced by the cell, which results in loss of other genes. Particularly, the virus genome causes a partial or complete loss of genes E1 and E2, which regulate the activity of genes E6 and E7. Therefore, without E1 and E2 regulation, E6 and E7 are able to be active and cause cancer in cells.
HPV integration can also stimulate overexpression of a gene called E2F1, which is a protein coding gene important for the cell cycle. Overexpression of this gene can cause uncontrolled growth of cells, which leads to tumor development and aneuploidy. Aneuploidy describes an irregular number of chromosomes in cells and is found in 90% of all tumors.
Evasion of Immune System
One trademark of cancer cells is their ability to evade attack by the immune system. The cells are able to do this through expression of certain proteins, known as immune inhibitory signaling proteins, which cause immune cell dysfunction. One of these proteins is known as programmed death-ligand-1 (PD-L1), which binds to immune cells and suppresses their function. Therefore, anti-PD-L1 antibodies have been used in some cancer treatments, in effort to suppress activity of PD-L1 and allow immune cells to function normally.
The 3 Biomarkers
One aspect of cancer genomics involves identifying molecules called biomarkers, which can be DNA, gene mutations, proteins, etc. that serve as indicators of underlying disease. Cancer biomarkers are useful in predicting how cancer will progress, and could help determine which treatment a specific patient’s cancer is likely to respond to. At Basin Genomics, we are currently working on developing a screening assay that can detect and quantify 3 biomarkers of HPV+ oral cancer. The 3 biomarkers we are targeting in our assay include:
E6, E7 mRNA Overexpression: Genes that are found in HPV+ cancer
DNA Index: Quantification of the DNA index and the percentage of cells in the proliferative stage of the cell cycle (Post G1)
PD-L1 Status: Provides prognostic information about immune cell functioning
Knowing which biomarkers are present in a patient can allow for physicians to design a more personalized treatment plan to most effectively treat the cancer.