EPIFY AIMS TO DRIVE EARLIER DETECTION AND MORE ACCURATE DIAGNOSIS, FACILITATING PERSONALIZED ONCOLOGY AND AN OPTIMAL OUTLOOK FOR CANCER

EPIFY AIMS TO DRIVE EARLIER DETECTION AND MORE ACCURATE DIAGNOSIS, FACILITATING PERSONALIZED ONCOLOGY AND AN OPTIMAL OUTLOOK FOR CANCER

ABOUT EPIFY

Epify was founded when a collaboration between Maastricht University and the bioinformatics group of Ghent University identified a need for their knowledge of epigenetic biomarkers to be translated into care for cancer patients. Epify will combine the scientific expertise from these institutions with a sound business knowledge to create industrial applications that ensure the biomarkers are used to their full potential and are made accessible to patients and clinicians.

Currently, the company is supported by Maastricht University and the head of the bioinformatics group of Ghent University, together with Novalis, a Belgian biotech incubator and Brightlands, regional shareholders based in the Limburg region of the Netherlands. Novalis made the cornerstone investment in the seeding round of the company.

WHAT IS EPIGENETICS?

DNA is present in every cell of all living organisms and contains the recipe for making proteins which determine what happens within the cell. Since all cells in an individual organism have the same DNA sequence, known as a genome, another factor is needed to control the diversity of appearance and function between genetically identical cells in different organs. This is where epigenetic modifications come into play. They change the structure of the DNA, thereby controlling the extent to which each gene is turned ‘on’ or ‘off’, and also playing a critical role in regulating DNA repair and replication.

  • DNA contains the recipe for making proteins which determine a cell’s structure and function.
    dna
  • The recipe is not fixed – epigenetic markers control the extent to which a gene is turned ‘on’ or ‘off’.

Types of epigenetic modification:

DNA Methylation

DNA methylation is the addition of a small compound, called a methyl group, at various points in the DNA sequence. Depending on where this occurs, methylation can either increase or inhibit gene expression.

Histone Modifications

Histone modifications alter how these DNA packaging proteins structure the DNA strands. This can alter how accessible certain genes are to the various DNA expression or repair mechanisms.

RNA Transcript Modifications

RNA transcript modifications also direct a cell’s behavior since RNA is responsible for carrying out the instructions encoded within the DNA.

ABOUT CANCER

The name cancer is given to a range of related diseases which are all essentially caused by a breakdown in control of the cell division process. Some of the body’s cells begin to divide in an uncontrolled manner and spread to surrounding tissues. Many types of cancer form a solid tissue mass, known as a tumor, but leukemias and other blood cancers do not.

Cancer has now taken over from heart disease as the leading cause of death in the Netherlands, and this shift is also fast approaching in many other high-income countries worldwide. This is primarily due to an increased life expectancy, together with improvements in treating heart disease, however the global incidence of cancer is still on the increase.

Cancer develops through stages in increasing severity, from being small and located in one area, to spreading to nearby tissues. The final stage, stage IV, means that the cancer has spread to other parts of the body, or metastasized. This stage can affect many different parts of the body and is the deadliest, therefore early detection is critical for the best patient outcome.

MARKET POTENTIAL

191 million patients are screened annually by biopsy. That’s about 11 times the population of the Netherlands. Of these, 2.6 million are diagnosed with cancer.

EPIGENETICS IN CANCER DIAGNOSIS

Cancer cells can contain many genetic (alterations in the DNA sequence) and epigenetic (DNA modification) changes. Epigenetic modifications are key in the transformation of normally-dividing cells to a cancerous state. In sporadic cancers, which are thought to constitute around 80% of all cancers, such alterations of genes involved in DNA repair or cell cycle control are common, and significantly more frequent than inherited mutations 1, 2. Therefore, epigenetics, and its manipulation, holds great promise for cancer prevention, detection and therapy 3, 4.

Certain epigenetic changes, known as biomarkers, are specific enough to be used for diagnosis or for discriminating between the various stages of cancer. Often, cancer in its earliest stage is caused by an increase in methylation of the activation mechanism of tumor suppressor genes, silencing them and creating conditions for uncontrolled cell division.

There is much research being carried out into the identification of diagnostic biomarkers in various types of cancer. The major advantage of this kind of screening is that the cancer can be identified from body fluids, eliminating the need for invasive tissue biopsies. Being able to detect these epigenetic changes can help in the diagnosis of cancer at an early stage, predicting the prognosis of a patient and selecting the right treatment.

BIOPSY

(Various Cancers)

BLOOD

(Various Cancers)

SPUTUM

(Lung Cancer)

URINE

(Bladder Cancer)

STOOL

(Colorectal Cancer)

EPIGENETICS AND CANCER TREATMENT

Epigenetic modifications are reversible, which makes them an excellent target for novel anticancer agents. This method has already shown great promise for certain cancers such as leukemias, colorectal cancer and brain tumors, and there are already some routinely used cancer treatments which act specifically on epigenetic modifications, with more in clinical trials.

Two drugs (5-azacytidine and 5-aza-20-deoxycytidine), which act on enzymes responsible for DNA methylation, have already been approved by the FDA for the treatment of various forms of cancer. They have been shown to reactivate antitumor systems that were repressed by the cancer, thereby enabling them to weaken the tumor 5, 6, 7, 8. Some success has also been observed with Zebularine, which activates a demethylation enzyme 9. Although these drugs significantly increase survival rates, they have wide ranging effects throughout the entire body, and therefore have major side effects when used for treatments.

Dietary polyphenols, such as those found in green tea and red wine, have also been linked to antitumor activity. An increased consumption has been shown to decrease global methylation rates and is therefore likely due to an epigenetic mechanism, however more research is needed in this area 10.

References

  1. Wood, LD et al. (2007) Science 318(5853): 1108-1113
  2. Jasperson, KW et al. (2010) Gastroenterology 138(6): 2044-2058
  3. Novak, K (2004) Medscape General Medicine 6(4): 17
  4. Banno, K et al. (2012) Int. J. Oncol. 41(3) 793-797
  5. Wells, RA et al. (2014) Current Oncology 21(1): 44-50
  6. Vendetti, TP et al. (2013) Expert Opinion on Biological Therapy 13(9): 1273-1285
  7. Hulli, L (2014) Oncotarget 5(3): 587-598
  8. Foulks, JM et al. (2012) Journal of Biomolecular Screening 17(1): 2-17
  9. Kowluru, RA et al. (2013) BioMed Research International: 635284
  10. Henning, SM et al. (2013) Epigenomics 5(6): 729-741