mutations correlate with the non-coding RNA content of small extracellular vesicles in melanoma.

Non-coding RNAs (ncRNAs) are important regulators of gene expression. They are expressed not only in cells, but also in cell-derived extracellular vesicles (EVs). The mechanisms controlling their loading and sorting remain poorly understood.

Use of non-small cell lung cancer multicellular tumor spheroids to study the impact of chemotherapy.

Background: Lung cancers represent the main cause of cancer related-death worldwide. Recently, immunotherapy alone or in combination with chemotherapy has deeply impacted the therapeutic care leading to an improved overall survival. However, relapse will finally occur, with no efficient second line treatment so far.

Prognostic Impact of TP53 Mutations in Metastatic Nonsquamous Non-small-cell Lung Cancer.

Background: The prognostic impact of TP53 mutations in advanced or metastatic nonsquamous non-small-cell lung cancer (nsNSCLC) patients treated with chemotherapy and/or immune checkpoint inhibitors (ICI) remains unclear.

Materials And Methods: We retrospectively collected data from patients with nsNSCLC treated in the first line from January 2018 to May 2021. The patient was separated into 2 groups according to their TP53 mutation status (wt vs.

The use of minimal residual disease in thoracic oncology: Gaps between promises and the on-the-ground reality of daily practice.

The assessment of minimal residual disease (MRD) from blood samples of patients with resected non-small cell lung carcinoma (NSCLC) is promising and opens up many opportunities for the optimisation of patient care in daily practice. Notably, this includes the potential for escalation or de-escalation of adjuvant therapies. Thus, the evaluation of MRD status can directly contribute to an increase in the overall survival of early stage NSCLC patients and/or limit therapeutic but also "financial" toxicity.

Implementation of circulating tumour DNA multi-target mutation testing in plasma: a perspective from an external quality assessment providers' survey.

Demand for large-scale tumour profiling across cancer types has increased in recent years, driven by the emergence of targeted drug therapies. Analysing alternations in plasma circulating tumour DNA (ctDNA) for cancer detection can improve survival; ctDNA testing is recommended when tumour tissue is unavailable. An online survey of molecular pathology testing was circulated by six external quality assessment members of IQN Path to registered laboratories and all IQN Path collaborative corporate members.

Metastatic pulmonary carcinoids with fusion response to ALK inhibitors: two case reports and review of literature.

Background: Pulmonary carcinoids (PC), including typical (TC) and atypical carcinoids (AC), are low-grade neuroendocrine tumors (NETs) which account for 1-5% of all lung tumors. Due to the low prevalence of PC and extreme rarity of anaplastic lymphoma kinase () rearrangements in patients with PC, the advances in targeted therapy development in PC are still limited and there is no standard treatment. Even though in patients with PC harboring rearrangements there is a room for a success in targeted therapy.

Results of a worldwide external quality assessment of cfDNA testing in lung Cancer.

Background: Circulating cell free DNA (cfDNA) testing of plasma for EGFR somatic variants in lung cancer patients is being widely implemented and with any new service, external quality assessment (EQA) is required to ensure patient safety. An international consortium, International Quality Network for Pathology (IQNPath), has delivered a second round of assessment to measure the accuracy of cfDNA testing for lung cancer and the interpretation of the results.

Methods: A collaboration of five EQA provider organisations, all members of IQNPath, have delivered the assessment during 2018-19 to a total of 264 laboratories from 45 countries.

HRAS Q61L Mutation as a Possible Target for Non-Small Cell Lung Cancer: Case Series and Review of Literature.

Introduction: Assessment of actionable gene mutations and oncogene fusions have made a paradigm shift in treatment strategies of non-small cell lung cancer (NSCLC). mutations involved around 0.2-0.

High efficacy of alectinib in a patient with advanced lung adenocarcinoma with 2 rare fusion sites: a case report.

Anaplastic lymphoma kinase () fusions have been identified in approximately 5% of non-small cell lung cancer (NSCLC) cases. ALK-tyrosine kinase inhibitors (TKIs) are the standard first-line treatment for patients with -positive (+) advanced NSCLC. Along with widespread use of next-generation sequencing (NGS) for the molecular diagnosis of lung cancer, an increasing number of fusion partners are being reported, with the majority being effective for ALK-TKIs.

Modulation of the Immune Response in Lung Cancer: From Biology to Therapeutic Impact.

The gene codes for liver kinase B1 (), a highly conserved serine/threonine kinase involved in many energy-related cellular processes. The canonical tumor-suppressive role for involves the activation of AMPK-related kinases, a master regulator of cell survival during stress conditions. In pre-clinical models, inactivation of leads to the progression of lung cancer with the acquisition of metastatic properties.

MEM: An Algorithm for the Reliable Detection of Microsatellite Instability (MSI) on a Small NGS Panel in Colorectal Cancer.

Purpose: MEM is an NGS algorithm that uses Expectation-Maximisation to detect the presence of unstable alleles from the NGS sequences of five microsatellites (BAT-25, BAT-26, NR-21, NR-24 and NR-27). The purpose of this study was to compare the MEM algorithm with a reference PCR method (MSI-PCR) and MisMatch Repair protein immunohistochemistry (MMR-IHC).

Methods: FFPE colorectal cancer samples from 146 patients were analysed in parallel by MSI-PCR and NGS using the MEM algorithm.

mutations in metastatic colorectal cancer: from a de facto ban on anti-EGFR treatment in the past to a potential biomarker for precision medicine.

Introduction: The high frequency of mutations, particularly mutations, in colorectal cancer (CRC) and the ineffectiveness of anti-EGFR antibodies in treating this disease has created a significant unmet medical need, especially for treating patients in the metastatic phase of this disease. There are many different types of mutations, the most frequent being G12V (c.35 G > T (p.

Detection of ALK fusion transcripts in plasma of non-small cell lung cancer patients using a novel RT-PCR based assay.

Background: Detection of genomic rearrangements, like anaplastic lymphoma kinase () fusions, is a pivotal requirement in non-small cell lung cancer (NSCLC) for the initiation of a targeted treatment. While tissue testing remains the gold standard, detection of these alterations using liquid biopsies is an unmet need. To enable the detection of rearrangements from circulating-free RNA (cfRNA) from NSCLC patients, we have evaluated a novel reverse transcription PCR (RT-PCR) based assay.

First-Line Afatinib plus Cetuximab for -Mutant Non-Small Cell Lung Cancer: Results from the Randomized Phase II IFCT-1503 ACE-Lung Study.

Purpose: Double inhibition of epidermal growth factor receptor (EGFR) using a tyrosine kinase inhibitor plus a monoclonal antibody may be a novel treatment strategy for non-small cell lung cancer (NSCLC). We assessed the efficacy and toxicity of afatinib + cetuximab versus afatinib alone in the first-line treatment of advanced -mutant NSCLC.

Patients And Methods: In this phase II, randomized, open-label study, patients with stage III/IV -positive NSCLC were randomly assigned (1:1) to receive afatinib (group A) or afatinib + cetuximab (group A + C).

Circulating Tumor DNA Early Kinetics Predict Response of Metastatic Melanoma to Anti-PD1 Immunotherapy: Validation Study.

The ability of early (first weeks of treatment) ctDNA kinetics to identify primary resistance to anti-PD1 immunotherapies was evaluated with a validation cohort of 49 patients treated with anti-PD1 for metastatic BRAF or NRAS-mutated melanoma, alone and pooled with the 53 patients from a previously described derivation cohort. BRAF or NRAS mutations were quantified on plasma DNA by digital PCR at baseline and after two or four weeks of treatment. ctDNA kinetics were interpreted according to pre-established biological response criteria.

Concomitant mutation status of -rearranged non-small cell lung cancers and its prognostic impact on patients treated with crizotinib.

Background: In non-small cell lung cancer (NSCLC), anaplastic lymphoma kinase () rearrangement characterizes a subgroup of patients who show sensitivity to tyrosine kinase inhibitors (TKIs). However, the prognoses of these patients are heterogeneous. A better understanding of the genomic alterations occurring in these tumors could explain the prognostic heterogeneity observed in these patients.

Mapping of colorectal carcinoma diseases with activation of Wnt/beta-catenin signalling pathway using hierarchical clustering approach.

Aims: To map the colorectal carcinoma (CRC) diseases with significant Wnt signalling pathway activation for delineating their clinicopathological and molecular profiles.

Methods: Mapping is based on hierarchical clustering analyses of a series of 283 CRCs. Data tabulated were histopathological patterns, immunophenotypic differentiation, , , mutations and microsatellite instability status, tumour-infiltrating lymphocytes (TILs) and genetic setting.

Osimertinib for Front-Line Treatment of Locally Advanced or Metastatic -Mutant NSCLC Patients: Efficacy, Acquired Resistance and Perspectives for Subsequent Treatments.

Non-small cell lung cancer (NSCLC) is one of the most efficient models for precision medicine in oncology. The most appropriate therapeutic for the patient is chosen according to the molecular characteristics of the tumor, schematically distributed between immunogenicity and oncogenic addiction. For this last concept, advanced NSCLC with epidermal growth factor receptor () mutation is one of the most illustrative models.

Circulating Tumor DNA as a Prognostic Determinant in Small Cell Lung Cancer Patients Receiving Atezolizumab.

Background: The IFCT-1603 trial evaluated atezolizumab in small cell lung cancer (SCLC). The purpose of the present study was to determine whether circulating tumor DNA (ctDNA), prospectively collected at treatment initiation, was associated with the prognosis of SCLC, and whether it identified patients who benefited from atezolizumab.

Methods: 68 patients were included in this study: 46 patients were treated with atezolizumab and 22 with conventional chemotherapy.