Helixbalance - Genomic Instability the first step

The main cause of genetic instability is the progressive accumulation of acquired (somatic) mutations in the DNA. This occurs when tumor suppressor genes fail to repair the damage caused by the thousands of lesions the DNA receives daily, resulting in somatic mutations. When these genes (tumour suppressors) stop working, the DNA damage is no longer repaired, leading to mutations progressively accumulating in the DNA. Maintaining the genome integrity by the DNA Damage Response (DDR) through tumor suppressor genes is critical to prevent cancer development. The DDR can induce apoptosis to eliminate damaged cells, promote DNA damage tolerance, activate checkpoints, and arrest the cell cycle progression to enable DNA repair, thus promoting genomic stability.

Detecting instability requires tracing the evolution of multiple subclones coexisting within a tumor, hence traditional tissue-based approaches are largely unfeasible. In a proof of principle study, we demonstrated the technical feasibility of extracting and analyzing healthy individuals’ cfDNA to detect genomic instability (Alborelli et al, Cell Death and Disease, 2019). The mutation rate in cfDNA is analyzed using Multi Biomarker Next Generation Sequencing (NGS) and sophisticated management software. Based on these and other subsequent results, we have developed the HELIXBALANCE genomic test as the first step of a “HELIXAFE cancer driver monitoring program”. HELIXAFE is based on the identification of progressive accumulations of mutations in the DNA repair genes, that can lead to genomic instability: BARD1; BLM; BRIP1; BUB1B; APOBEC3B; ATM; ARID1A; ATR; ARID1B; ATRX; ARID2; AXIN1; CDK12; CDKN2A; CHEK2; CTNNB1; DICER1; MLH1; FANCD2; MSH2; FOXA1; MSH6; KMT2D; NFE2L2; PMS2; RAD21; RECQL4; TP53 (limit of detection 0,2 %) to assess the prodromal, totally asymptomatic, stage of solid cancer (brain excluded).

CYTOBALANCE, IMMUNEBALANCE, and MICROBALANCE for tissue macro-environment analysis.
HELIXBALANCE for genomic instability is followed by analysing alterations in the tissue microenvironment where the cancer will probably develop. These steps following the HELIXAFE monitoring program (CYTOBALANCE, IMMUNEBALANCE, MICROBALANCE) allow the detection of the secondary cancer drivers (chronic inflammation, immune system imbalance, and altered microbiota), known to provide a favourable environment for the transition from premalignancy to malignancy. They can both promote genomic instability or insist on it, resulting in cancer risk amplification. Inflammatory cells may produce molecules, such as reactive oxygen species (ROS), that can lead to DNA damage and mutations. Immune cell imbalance can halt the ability of the body’s natural defences to kill cancer cells. The imbalance of the human microbiota, so-called dysbiosis, can be linked to carcinogenesis. With HELIXAFE, BIOSCIENCE GENOMICS proposes a program that enables actionable colorectal cancer driver interception and management, starting from monitoring the factors promoting genomic instability, the primary driver of cancer development. For each driver condition, our company will recommend specific chemo-preventive biologic agents (e.g., vitamins, food supplements), allowing individuals to act before the cancer onset to counteract the disease already from its physiopathologic stage, way before early diagnosis.

The HELIXAFE innovation is ground-breaking. Its multiple-tests program allows the interception of genomic instability drivers and the assessment of the prodromal, totally asymptomatic stage of colorectal cancer. By performing periodic, non-invasive, and non-risky screening tests, we can monitor genomic instability, intercept signs of colorectal cancer driver presence, and suggest totally personalized chemo-preventing measures to reduce the risk of its development. Shifting the focus from early-stage cancer detection to cancer driver interception and early management represents a drastic change of perspective for the entire society. Nowadays, colorectal cancer screening tools enable cancer identification only when it is already present. HELIXAFE anticipates early detection several years in advance, also thanks to the optimization of the AI algorithm, which will be constantly fed with the multiple data from periodic screenings.
HELIXAFE is not another genetic test for colorectal cancer risk detection: we do not aim at informing individuals that, sooner or later, they may develop colorectal cancer. The common perception of genetic tests for cancer prevention is that they are useless, as they indicate a predisposition to the potential development of a tumor. This condition cannot be modified. The reason is that these tests are based on the analysis of germline (inherited) mutations. HELIXAFE, instead, analyzes physiological conditions which become drivers of cancer when altered, which are modifiable with the adoption of chemo-preventive treatments and lifestyle habits change. The results obtained through HELIXAFE are a really useful answer for both the patient and the physician because they detect pathophysiological conditions that can always be treated with standard, non-invasive interventions without side effects.