Lectures' Abstracts
Overview of CTCs: approaches, disease monitoring and early detection of cancer and use in clinical practice in Europe
Catherine Alix-Panabières | Universitè de Montpellier, Montpellier, France
Dr. Alix-Panabiere is an expert in liquid biopsies and a partner of the PANTHER (FUI project) as well as big European projects in this area, including CTC-SCAN (Transcan project), CANCER-ID (IMI project), PROLIPSY (Transcan project) and European Liquid Biopsy Academy (ELBA, Marie-Curie project). In her talk, she will present and discuss the available technologies to isolate and evaluate CTCs, as the use of CTCs in the clinical practice in Europe.
Detection of BRAFV600E mutation in lymphatic drainage-derived extracellular vesicles as prognostic factor and residual disease indicator in melanoma
Susana García-Silva | Spanish National Cancer Research Center (CNIO), Madrid, Spain
Liquid biopsies in cancer patients have the potential to implement more precise tools for diagnosis and prognosis and thus, they could facilitate the implementation of a personalized medicine. Exudative seroma obtained from the drainage-implanted post-lymphadenectomy in melanoma patients has never been explored as a source of biomarkers. In addition to circulating tumor cells (CTCs) and tumor DNA (ctDNA), the use of circulating extracellular vesicles (EVs) is emerging as an additional source of surrogate markers of tumor progression, and might be a powerful non-invasive tool in this setting. Dr. García-Silva will present results showing for the first time that exudative seroma obtained post-lymphadenectomy is a novel biofluid enriched on EVs and DNA that can be interrogated for melanoma markers and BRAF mutation. This novel approach might aid oncologists to identify high-risk patients’ post-lymphadenectomy and improve their outcome by providing specific adjuvant therapies right after surgery.
Liquid biopsies components as surrogates for cancer treatment response
Diana Noronha Nunes | A. C. Camargo Cancer Center, São Paulo, Brazil
The availability of biomarkers that allow early detection, track tumor recurrence and therapeutic response, is of utmost importance. In this scenario, the three components of liquid biopsy – tumor-derived cell free DNA (ctDNA); extracellular vesicles (EVs) and circulating tumor cells (CTCs) - are promising tools for liquid biopsies, as it enables monitoring of tumor dynamics and reveal a broader picture of tumor heterogeneity. In this context, I will present results generated in the Medical Genomics Laboratory in A.C. Camargo, where we evaluate the liquid biopsies components with a special interest in survey the patient’s response to therapy, either in breast, gastric and colorectal carcinoma.
Circulating non-coding RNAs as tumor biomarkers
Miriam Galvonas Jasiulionis | Universidade Federal de São Paulo, São Paulo, Brazil
The efficiency of cancer treatment can be greatly improved by the development of diagnostic and prognostic biomarkers for early and precise detection, monitoring tumor recurrence and progression after treatment. Non-coding RNAs (ncRNAs), including micro-RNAs (miRNAs) and long non-coding RNAs (lncRNAs), present their expression altered in tumors, which contribute to the different hallmarks of cancer. These molecules can be also found in the blood and non-blood body fluids, both free and into extracellular vesicles. Considering their abundance and stability, circulating ncRNAs are promising tumor biomarkers. Recent advances and perspectives in the use of circulating ncRNAs as diagnostic and prognostic biomarkers for different types of cancer will be discussed.
Circulating microRNAs as potential biomarkers for early detection in lung cancer
Patrícia Pintor dos Reis | Universidade Estadual Paulista, Botucatu, Brazil
MicroRNAs (miRNAs) are potent gene expression regulators. Deregulated miRNA expression levels are associated with cancer development and progression. miRNAs are small, highly stable molecules that can be easily detected in body fluids. In fact, miRNAs are abundant in blood plasma. Such characteristics make miRNAs ideal candidates as circulating biomarkers with potential clinical use. In cancer, such molecules are currently being investigated towards applications to improve diagnosis, early detection, and for monitoring disease and therapeutic responses. In this lecture, we will focus on early detection of lung cancer. Late diagnosis of lung carcinoma remains as an important clinical problem and is often associated to treatment failure and patient death. Therefore, development of early detection biomarkers can lead to improvement in survival. We developed a preliminary study in a cohort of Canadian patients and identified circulating miRNA signatures in plasma from patients with lung adenocarcinoma and squamous cell carcinoma, compared to non-diseased controls. miRNA signatures were determined by expression analysis of an 800-miRNA panel in the Nanostring nCounter® platform. Data were confirmed in an independent patient set, by TaqMan quantitative PCR assays specific to 12 unique miRNAs included in three distinct signatures. In addition, computational analyses identified significantly enriched pathways modulated by three miRNAs in the most robust signature. Notably, miRNA-regulated pathways were associated with lung tumorigenesis. Our future directions include validation of miRNA signatures in a larger sample set from a geographically distinct, Brazilian population.
The growing relevance of liquid biopsy in clinical research: available technologies and recent advances
Beatriz Pinto | Thermo Fisher Scientific, São Paulo, Brazil
At this symposium, Beatriz Pinto will present the main reasons why liquid biopsy has become increasingly relevant in the clinical environment, the cutting-edge tools, solutions and technologies in Next Gen Sequencing available today to investigate mutations in free nucleic acids in blood, and some outstanding publications in this area.
Could circulating tumor DNA underpin the precision medicine?
Danielle Queiroz Calcagno | Universidade Federal do Pará (UFPA), Belém, Brazil
In the last years, circulating tumour DNA (ctDNA) has emerged as a potential minimally invasive ‘liquid biopsy’ tool in precision medicine. ctDNA refers to genomic DNA fragments that are released into the bloodstream after the active secretion of microvesicles, apoptosis or necrosis. These fragments reflect tumor evolution and genomic alteration present in primary and/or metastatic tumor. Notably, a ctDNA analysis might allow the stratification of patients, the monitoring of the therapeutic response, and the establishment of an opportunity for early intervention independent of detection by imaging exams or clinical symptoms. The present lecture will address the evidence on the potential role of ctDNA in supporting individualized clinical treatment decisions for patients with melanoma, castration-resistant prostate cancer, breast cancer, metastatic colorectal cancer, and non-small cell lung cancer.
ddPCR liquid biopsy’s impact on precision medicine
André Lavorato | Bio-Rad Laboratories, São Paulo, Brazil
Precision medicine has advanced significantly in the past years. We passed from a yes or no answer to the ability to measure, make choices and follow progress of almost any disease. Moreover, we can distinguish the disease profile, the aggressiveness, when is it gone and when is returning. Newer technologies, such as ddPCR, evolved to detect very low amounts of DNA, allowing the analysis of cell-free DNA (cfDNA) in blood of the patients. In this lecture, it will be discussed how medicine can apply it to: disease detection, directing therapy choices, screening, and prognostic; response, choosing neoadjuvants, adjuvants, dose, and surgery; and monitoring, tracking resistance, recurrence, and relapse.
Circulating tumor DNA assays in clinical diagnostic tests
Elisa Ferreira | Fleury Group, São Paulo, Brazil
The possibility of investigating genetic information derived from solid tumors via plasma or other body fluids has led to the development of minimally invasive diagnostics approaches, named liquid biopsy. Liquid biopsies consist on the detection and isolation of circulating tumor cells (CTCs), circulating vesicles, such as exosomes, or cell free circulating tumor DNA/RNA (ctDNA/ctRNA), that are short fragments of nucleic acids released from tumor cells undergoing apoptosis and necrosis. The use of ctDNA for molecular profiling of tumors is especially promising in poorly accessible tumors and as an alternative for small tissue biopsies. Nonetheless, given the fragmented pattern of ctDNA and the usually low quantities of ctDNA shedding, the development of high accurate diagnostic tests is a huge challenge. Different strategies are being used for ctDNA evaluation. Next generation sequencing is a comprehensive approach that can detect different mutations in a single test; however, it depends on deep-sequencing and complex bioinformatics analysis for correctly identifying variants with low allele frequencies. On the other hand, digital PCR is a highly sensitive, cost-effective and a streamlined technique that needs lower quantities of ctDNA and is intended to the analysis of a few hotspots at a time. In this talk, the challenges of developing and validating diagnostic tests for the analysis of ctDNA will be discussed, as well the experience of Fleury Group in implementing liquid biopsies tests for detection of hotspots mutations in EGFR oncogene.
OUR SPONSORS
