Skip to main content
0

Cancer driver interception is the new approach to cancer prevention that enables taking action against the disease well before its development. You can implement it by monitoring your genome instability. Let’s discover what is and how to counteract it with HELIXAFE, Bioscience Institute’s solution for cancer driver interception.

Cancer has its roots in our genes: the genome alterations occurring throughout life, following exposure to other cancer risk factors, make cells grow abnormally, invading tissues and organs, and spreading to other body parts.

The progressive accumulation of somatic (non-inherited) mutations is indicative of genome (or genomic, or genetic) instability and can lead to cancer. In fact, genome instability is the first cancer driver. It is not a marker of the risk of cancer, but an indicator of the cancer prodromal stage.

What is more, genomic instability is preventable and actionable; that is, it is the ideal target for a cancer driver interception program.

What is cancer driver interception?

Cancer driver interception refers to the interruption of carcinogenesis before the development of the disease and of its symptoms, in healthy people. In particular, during the so-called cancer prodromal stage, cells accumulate somatic mutations at a rate displaying genome instability.

Genome instability naturally arises over a timespan ranging from years to decades, during which the vast majority of cells that acquired it die, and probably are cleared away by the immune system. However, if an even minimal fraction of cells that have acquired genomic instability are not cleared away, they can eventually give rise to a tumor.

Why is genome instability linked to cancer?

The causes of genome instability lie in the constant threat under which DNA integrity is. Damage can arise from both endogenous and exogenous factors, such as:

  • spontaneous DNA damaging events; for example, modification of DNA bases, or generation of DNA breaks by reactive oxygen species produced by the normal cell metabolism
  • exposure to external agents; for example, ultraviolet (uv) rays, or genotoxic chemicals
  • failure in cellular DNA processing and replication.

Genome instability is a matter of rate

Genome instability emerges as a progressive accumulation of somatic mutations; that is, acquired, non-heritable, changes in DNA sequence in cells other than the cells that will give rise to sperm or eggs (germ cells).

Somatic mutations occur after conception, cannot be passed onto offspring, and develop in specific tissues (for example, the breast or lung). In contrast, germline mutations are inherited mutations that are passed onto every cell of the offspring.

Only a limited percentage of cancers have a clear hereditary component, and even in those cases in which cancer susceptibility is clearly inherited, somatic, acquired mutations are needed for cancer to develop.

However, the simple presence of genetic alterations, even when frequent, is not a marker of genetic instability. In fact, by definition, instability is a matter of rate. That is why simple analysis of the presence of somatic mutations cannot be used to determine genetic instability.

How to assess genome instability

Compared to healthy people’s blood, cancer patients’ blood typically presents higher levels of total circulating cell-free DNA (cfDNA); that is, small DNA fragments. It also contains a limited amount of circulating-tumor DNA (ctDNA) – no more than 10% of total cfDNA.

Researchers already gave proof of concept that genomic instability analysis in blood cfDNA samples is a feasible approach to assess the cancer prodromal stage. Now, Bioscience Institute‘s startup, Bioscience Genomics, offers a five-test program enabling the interception of both genomic instability and their drivers.

«HELIXAFE allows for identifying mutations that promote genome instability and obtaining a trend of stability for solid cancer associated mutations. All that is required is a 10-20 cc blood sample, from which cfDNA is obtained» Armando Castiello, Branch Manager at Bioscience Genomics, explains.

«A single high mutation frequency can be a random error causing incorrect evaluations. That is why to accurately evaluate genome instability in an individual, samples from at least two time points are needed. Only a somatic mutation frequency growth trend, manifested over a prolonged period, is indicative of genomic instability».

Based on the HELIXAFE algorithm, if there are no mutations in cfDNA, or if mutations in cfDNA are also detected in white blood cells’ DNA (germline control), all that is needed is to schedule the next check-up in one year; in fact, the presence of a mutation in the germline control means that it is an inherited (not acquired) mutation, not indicative of genome instability.

Mutations in cfDNA that are not detected in the germline control are somatic mutations. In such a case, germline mutations in cancer susceptibility genes should also be tested, looking for genes that can promote cancer development in the presence of somatic mutations.

The first level HELIXAFE prevention program (HELIXBALANCE) looks for mutations responsible for genome instability. Analyzed genes include factors involved in DNA damage and/or repair, chromatin remodeling or DNA methylation, β-catenin/WNT signaling, and cell cycle control.

The second level HELIXAFE prevention programs are:

  • HELIXPAN: to identify the tissues and organs that need targeted prevention from somatic mutations linked to genome instability; suitable for people at a low risk for solid cancer. If detected mutations are in lung, colon or breast-associated genes, screening for low-frequency somatic mutations with one of the three more specific programs (HELIXMOKER, HELIXCOLON or HELIXGYN) is recommended.
  • HELIXMOKER: to analyze genes involved in respiratory system cancers; specifically designed for smokers and highly pollution-exposed subjects.
  • HELIXCOLON: to analyze genes colon cancer; suitable for people at increased colorectal cancer risk.
  • HELIXGYN: suitable for women exposed to hormone therapies or at a high risk for breast or ovarian cancer because of BRCA 1 or 2 mutations.

When should you start cancer driver interception?

Aging is the most important cancer risk factor, but genetic instability develops well before the disease and its symptoms. Also, cancer can occur at all ages. That means that it is never too soon to start cancer driver interception.

For more information about HELIXAFE, please visit Bioscience Institute’s webpage or feel free to contact us at info@bioinst.com. Our biologist will answer your questions with no commitment on your part.

References

  • Alborelli et al. Cell-free DNA analysis in healthy individuals by next-generation sequencing: a proof of concept and technical validation study. Cell Death Dis.. 2019 Jul 11;10(7):534. doi: 10.1038/s41419-019-1770-3
  • Beane j et al. Genomic approaches to accelerate cancer interception. Lancet Oncol. 2017 Aug;18(8):e494-e502. doi: 10.1016/S1470-2045(17)30373-X
  • Blackburn EH. Cancer Interception. Cancer Prev Res (Phila). 2011 Jun;4(6):787-92. doi: 10.1158/1940-6207
  • Ciccia A and Elledge SJ. The DNA Damage Response: Making it safe to play with knives. Mol Cell. Mol Cell. 2010 Oct 22; 40(2): 179–204. doi: 10.1016/j.molcel.2010.09.019
  • Ferguson LR et al. Genomic instability in human cancer: Molecular insights and opportunities for therapeutic attack and prevention through diet and nutrition. Semin Cancer Biol . 2015 Dec;35 Suppl(Suppl):S5-S24. doi: 10.1016/j.semcancer.2015.03.005
  • Niedernhofer LJ et al. Nuclear Genomic Instability and Aging. Annu Rev Biochem. 2018 Jun 20;87:295-322. doi: 10.1146/ annurev-biochem-062917-012239
Share on:
Close Menu