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Fighting cancer through research

Selection pressures exerted by therapeutic agents operate on the phenotypic variability acquired by the accumulation of genetic and epigenetic alterations during tumor evolution.

The aim of the TRACEPIGEN project is to develop and standardize a new pipeline for ultra-sensitive targeted cfDNA sequencing using single-step target enrichment and library preparation method that will allow us to test for the presence of variant DNA methylation marks and somatic mutations at single base resolution in minute quantities of cfDNA.

The standardized pipeline will be applied on prospectively collected serial plasma cfDNA samples from patients diagnosed with advanced stage colorectal (CRC) and non-small cell lung cancer (NSCLC) to evaluate the dynamics of genetic and epigenetic alterations in relation to therapy outcomes and the potential for earlier detection of drug therapy failure.

Precision Medicine

Even though the spectrum of available targeted therapies for different cancers is wide, major clinical challenge stemming from tumor phenotypic heterogeneity and clonal evolution is acquired resistance to systemic drug therapy. TRACEPIGEN project is going to address the underlying mechanisms for relapse and resistance that occur in the patients with lung and colorectal cancers after previous good response to the first-line therapy.

Most of the lung and colorectal cancers are discovered in the advanced stages when they are inoperable and, after the first-line treatment, they continue to grow and to endanger patient’s life.  Recent cancer genomics studies provided deeper insight into intra- and inter-tumoral heterogeneity, demonstrating that most cancers are composed of several genetic subpopulations and the major clinical challenge stemming from tumor phenotypic heterogeneity and clonal evolution is acquired resistance to systemic drug therapy.

TRACEPIGEN project aims to investigate genetic and epigenetic changes in lung and colorectal cancers during the course of systemic treatment that are related to therapy resistance and cause disease progression.

Molecular Tumor Profiling

The beginning of the 21st century and the discovery of the whole sequence of the human genome represents one of the major milestones in the history of human genetics. This discovery has marked the beginning of the new era of genomics that yielded important research and shed the new light on molecular mechanisms that lead to the cancer development. Thanks to the development of massive parallel sequencing and other high throughput genomic technologies new drugs have been developed which are able to target tumor cells without affecting the rest of the healthy tissues unlike conventional chemotherapy approaches.

Cancer precision medicine is defined as “the use of therapeutics that are expected to confer benefit to a subset of patients whose cancer displays specific molecular or cellular features (most commonly genomic changes and changes in gene or protein expression patterns” (more info here). In certain tumors, molecular profiling may yield clinically relevant diagnostic and prognostic information. Precision medicine has already transformed cancer care: both common and rare malignancies can be targeted by specific therapies to improve clinical outcomes in patients.

Liquid Biopsies

Owing to their invasive nature, repeated tumor biopsies cannot always be performed in the clinical setting, and are also liable to sampling bias. Liquid biopsies, comprising the noninvasive analysis of circulating tumor-derived material, represent an innovative tool in precision medicine to overcome current limitations associated with standard tissue biopsies (more info here). Liquid biopsies in the form of cfDNA isolated from blood plasma have shown great promise to be used as minimally-invasive markers in cancer patients providing an insight into the composition of both primary tumor and metastases, and an opportunity to assess clonal dynamics throughout the course of disease. Presence of detectable cfDNA was demonstrated even in early stage tumors, and several studies demonstrated the utility of cfDNA for monitoring tumor dynamics during treatment in patients with advanced carcinomas by both targeted and whole exome sequencing of cfDNA (more info here). CfDNA carries not only tumor-specific changes in its sequence but also distinctive epigenetic marks, namely DNA methylation patterns reflecting those of the primary tumor (more info here).

The extent to which noninvasive methods might ultimately replace standard tissue biopsies is still unclear. For diagnosing primary tumors or determining the stage of metastatic lesions in tissues where it is difficult to extract a sample, liquid biopsy might provide a reliable alternative. Liquid biopsy could also help to avoid complications that occur after invasive tissue biopsy, such as bleeding, infections and pain.

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