5th August 2019

Expert Advice: The Expanding Molecular Diagnostic Approach in Cancer Treatment

Over the past decade, genetic testing has become an essential component of the management of solid and hematologic cancers. It is estimated that 50-90% of tumours bear one or more ‘actionable’ mutations, which could be targeted with either EMA-approved or experimental drugs. As new technologies allow for more and more genes to be tested simultaneously (up to the whole genome), the clinical utility of the information collected becomes even more relevant.

The early approach to gene testing was to look for one or few selected mutations, based on a patient’s personal and familiar history; the strict criteria guaranteeing the clinical utility of endorsed genetic tests ensured that matching of the cancer’s driver mutation with appropriate targeted therapy was straightforward. This approach, however, had the limitation of excluding many patients potentially benefiting from genetic testing and many mutations potentially relevant for cancer management.

The widespread transition from Sanger sequencing to next-generation sequencing (NGS), along with diffusion of big data analysis and machine learning, ushered in a new era of genetic testing in oncology; an era where less expensive and faster analytical techniques allow for ever larger multi-gene panels, and bioinformatic algorithms help translate the massive amount of data generated into clinically meaningful information.

Comprehensive genomic profiling and whole genome sequencing still lack sufficient consensus, concerning data interpretation and appropriate mutation-therapy matching, to be routinely implemented in clinical practice. However, it is crucial that national and international studies are set up to investigate how the interaction of different cancer mutations determines tumour aggressiveness, and thus influences therapeutic response; the possibility of yet-uncovered driver mutations that could help further our understanding of cancer development, and be included in preventive and therapeutic strategies, should also be explored. The role of TMB (tumour mutation burden) and other genetic biomarkers in cancer immunotherapy are also being investigated through comprehensive genomic profiling, and are likely to become crucial in predicting response to immunotherapy and guiding therapeutic choices.

Kelyon has always been at the forefront of precision oncology, pioneering the use of the hub-and-spoke distribution system, to connect hospitals to certified laboratories carrying out genetic tests (such as BRCA, EGFRand RAS). Kelyon also provides the digital infrastructure for the Association of Medical Oncology’s quality control programme (Biogate) for the validation and certification of molecular diagnostics laboratories in Italy.

Kelyon is now raising the bar by partnering up with national and regional stakeholders on a series of projects aimed at building a comprehensive database of ‘actionable’ mutations in cancer patients; this will create the bioinformatics infrastructure to analyze the collected data and eventually provide clinicians with a ‘genetic cancer blueprint’ and report of optimal treatment options tailored to each patient’s cancer DNA profile.

As the United Kingdom has always been at the cutting edge of medical innovation and research, Kelyon is looking forward to export its expertise, and collaborate with UK hospitals, universities and pharma companies to progress the next phase of cancer patient management.