Eloisa Jantus

• PhD
• Head of Department at Fundación Hospital General Universitario de Valencia

Predicting response to targeted cancer therapies increasingly relies on both simple and complex genetic biomarkers. Comprehensive genomic profiling using high-throughput assays must be evaluated for reproducibility and accuracy compared with existing methods. This study is a multicenter evaluation of the Oncomine™ Comprehensive Assay Plus (OCA Plus...

The treatment of non-small cell lung cancer (NSCLC) patients has significantly improved with recent therapeutic strategies; however, many patients still do not benefit from them. As a result, new treatment approaches are urgently needed. In this study, we evaluated the antitumor efficacy of co-targeting G9a and DNMT1 enzymes and its potential as a...

Immunotherapy has opened new avenues of treatment for patients with advanced non-small cell lung cancer (NSCLC) without previous hope of survival. Unfortunately, only a small percentage of patients benefit from it, and it is still not well understood which tumor characteristics can be used to predict immunotherapy response. As the key cellular effe...

Background KRAS- mutant non-small cell lung cancer (NSCLC) shows a relatively low response rate to chemotherapy, immunotherapy and KRAS -G12C selective inhibitors, leading to short median progression-free survival, and overall survival. The MET receptor tyrosine kinase (c- MET ), the cognate receptor of hepatocyte growth factor (HGF), was reported...

Purpose High-mobility group box 1 protein (HMGB1) is subject to exportin 1 (XPO1)-dependent nuclear export, and it is involved in functions implicated in resistance to immunotherapy. We investigated whether HMGB1 mRNA expression was associated with response to immune checkpoint inhibitors (ICI) in non-small cell lung cancer (NSCLC). Patients and M...

Immunotherapy has been proven a viable treatment option for non-small cell lung cancer (NSCLC) treatment in patients. However, some patients still do not benefit. Finding new predictive biomarkers for immunocheckpoint inhibitor (ICI) response will improve treatment management in the clinical routine. In this regard, liquid biopsy is a useful and no...

Drug combinations are key to circumvent resistance mechanisms compromising response to single anti-cancer targeted therapies. The implementation of combinatorial approaches involving MEK1/2 or KRASG12C inhibitors in the context of KRAS-mutated lung cancers focuses fundamentally on targeting KRAS proximal activators or effectors. However, the antitu...

Despite the success of therapies in lung cancer, more studies of new biomarkers for patient selection are urgently needed. The present study aims to analyze the role of galectin‐3 (GAL‐3) in the lung tumor microenvironment (TME) using tumorspheres as a model and explore its potential role as a predictive and prognostic biomarker in non‐small cell l...

Synthetic biology aims to program living bacteria cells with artificial genetic circuits for user-defined functions, transforming them into powerful tools with numerous applications in various fields, including oncology. Cancer treatments have serious side effects on patients due to the systemic action of the drugs involved. To address this, new sy...

Lung oncogenesis relies on intracellular cysteine to overcome oxidative stress. Several tumor types, including non-small cell lung cancer (NSCLC), upregulate the system xc- cystine/glutamate antiporter (xCT) through overexpression of the cystine transporter SLC7A11, thus sustaining intracellular cysteine levels to support glutathione synthesis. Nuc...

Resistance mechanisms compromise response to single targeted therapies, favoring the idea that combinatorial strategies are key to circumvent this clinical problem. Combinatorial strategies for cancers driven by oncogenic KRAS based on MEK1/2 or KRASG12C inhibitors have so far incorporated abrogation of KRAS proximal effectors involved in oncogenes...

10507 Background: Tobacco is the main risk factor for developing lung cancer. Yet, while some heavy smokers develop lung cancer at young age others never develop it, even at advanced age. This suggests a remarkable variability in the individual susceptibility to the carcinogenic effects of tobacco. We characterized the germline profile of subjects...

The role of dysbiosis in the development and progression of oral potentially malignant disorders (OPMDs) remains largely unknown. Here, we aim to characterize and compare the oral microbiome of homogeneous leucoplakia (HL), proliferative verrucous leukoplakia (PVL), oral squamous cell carcinoma (OSCC), and OSCC preceded by PVL (PVL-OSCC). Fifty ora...

Despite the durable responses provided by the introduction of checkpoint inhibitors in advanced Non-Small Cell Lung Cancer (NSCLC) without actionable targets in a subset of patients, a large proportion of them will progress after immunotherapy. Programmed Death Ligand 1 (PD-L1) was the first biomarker approved for immunotherapy, although it has mul...

Background: Mutations and deregulations in components of the Hedgehog (Hh) pathway have been associated with cancer onset and tumor growth in different malignancies, but their role in non-small cell lung cancer (NSCLC) remains unclear. This study aims to investigate the expression pattern of the main components of the Hh pathway in tumor and adjac...

Lung cancer is a malignant disease with high mortality and poor prognosis, frequently diagnosed at advanced stages. Nowadays, immense progress in treatment has been achieved. However, the present scenario continues to be critical, and a full comprehension of tumor progression mechanisms is required, with exosomes being potentially relevant players....

Introduction : In the current era of personalized medicine, liquid biopsy has acquired a relevant importance in patient management of advanced stage non-small cell lung cancer (NSCLC). As a matter of fact, liquid biopsy may supplant the problem of inadequate tissue for molecular testing. The term “liquid biopsy” refers to a number of different biol...

Finding angiogenic prognostic markers in advanced non-small-cell lung cancer is still an unmet medical need. We explored a set of genetic variants in the VEGF-pathway as potential biomarkers to predict clinical outcomes of patients with non-small-cell lung cancer treated with chemotherapy plus bevacizumab. We prospectively analyzed the relationship...

Objectives: Oral microbiome plays an important role in oral diseases. Among them, proliferative verrucous leucoplakia (PVL) is an uncommon form of progressive multifocal leukoplakia with a worryingly rate of malignant transformation. Here, we aimed to characterize the oral microbiome of PVL patients and compare it with those of healthy controls....

Introduction: Immune checkpoint inhibitors (ICIs) have demonstrated clinical efficacy in non-small cell lung cancer (NSCLC) patients (p). However, ICIs can also trigger a self-reactive response in the adjacent healthy lung tissue that can eventually lead to life-threatening immune-related adverse events (irAEs), like checkpoint inhibitor pneumoniti...

Despite impressive and durable responses, non‐small cell lung cancer (NSCLC) patients treated with anaplastic lymphoma kinase inhibitors (ALK‐Is) ultimately progress due to development of resistance. Here, we have evaluated the clinical utility of circulating tumor DNA (ctDNA) profiling by next‐generation sequencing (NGS) upon disease progression....

Simple Summary Apart from genetic changes, cancer is characterized by epigenetic alterations, which indicate modifications in the DNA (such as DNA methylation) and histones (such as methylation and acetylation), as well as gene expression regulation by non-coding (nc)RNAs. These changes can be used in biological fluids (liquid biopsies) for diagnos...

Despite the success of immunotherapies in lung cancer, development of new biomarkers for patient selection is urgently needed. This study aims to explore minimally invasive approaches to characterize circulating T cell receptor beta chain (TCR-β) repertoire in a cohort of advanced non-small cell lung cancer (NSCLC) patients treated with first-line...

INTRODUCTION KRAS mutations, the most frequent gain-of-function alterations in NSCLC, are currently emerging as potential predictive therapeutic targets. The role of KRAS-G12C (Kr_G12C) is of special interest after the recent discovery and preclinical analyses of two different Kr_G12C covalent inhibitors (AMG-510, MRTX849). METHODS KRAS mutations w...

Background: The human gut harbors around 1013-1014 microorganisms, collectively referred to as gut microbiota. Recent studies have found that the gut microbiota may have an impact on the interaction between immune regulation and anti-cancer immunotherapies. Methods: In order to characterize the diversity and composition of commensal microbiota a...

Background Survival data support the use of first-line osimertinib as the standard of care for epidermal growth factor receptor (EGFR)–positive non-small cell lung cancer (NSCLC). However, it remains unclear whether upfront osimertinib is superior to sequential first- or second-generation tyrosine kinase inhibitors (TKIs) followed by osimertinib fo...

This study aimed to investigate the role of a panel of salivary cytokines as biomarkers for early detection oral squamous cell carcinoma (OSCC), comparing their levels among healthy individuals, patients with oral leukoplakia (OL), and malignant lesions. Cytokine profiling analysis performed in a minimally invasive sample was correlated with clinic...

Objectives: To explore the pathophysiology of proliferative verrucous leucoplakia (PVL) through a methylated DNA immunoprecipitation and high-throughput sequencing (MeDIP-seq) case-control study. Materials and methods: Oral biopsies from ten PVL patients and five healthy individuals were obtained and used to compare their epigenetic patterns. Ne...

Introduction KRAS mutations, the most frequent gain-of-function alterations in non-small cell lung cancer (NSCLC), are currently emerging as potential predictive therapeutic targets. KRAS-G12C (Kr_G12C) role is of special interest, following the recent discovery and preclinical analyses of two different Kr_G12C covalent inhibitors (AMG-510, MRTX849...

Two-dimensional (2D) in vitro cell cultures and laboratory animals have been used traditionally as the gold-standard preclinical cancer model systems. However, for cancer stem cell (CSC) studies, they exhibit notable limitations on simulating native environment, which depreciate their translatability for clinical development purposes. In this study...

Introduction Precision medicine is already a reality in the field of oncology given that the selection and use of biomarker-driven therapies has clearly improved patient survival. Furthermore, a new, minimally invasive strategy termed ‘liquid biopsy’ (LB) has revolutionized the field by allowing comprehensive cancer genomic profiling through the an...

Several platforms for non‐invasive EGFR testing are currently used in the clinical setting with sensitivities ranging from 30% to 100%. Prospective studies evaluating agreement and sources for discordant results remain lacking. Herein, 7 methodologies including two next‐generation sequencing (NGS)‐based methods, three high‐sensitivity PCR‐based pla...

Background: Despite impressive and durable responses, patients treated with ALK inhibitors (ALK-Is) ultimately progress. We investigated potential resistance mechanisms in a series of ALK-positive non-small cell lung cancer (NSCLC) patients progressing on different types of ALK-Is. Methods: 26 plasma and 2 cerebrospinal fluid samples collected upon...

Tumors are complex tissues in which cancer cells are interwoven with fibroblasts, endothelial cells, pericytes, and inflammatory cells; these cells and the extracellular matrix constitute the tumor microenvironment (TME). The TME can modulate the behavior of tumor cells in terms of capacity to invade neighboring or distant tissues and drug resistan...

Background: The study of immune surveillance in the tumour microenvironment is leading to the development of new biomarkers and therapies. The present research focuses on the expression of CD5 and CD6-two lymphocyte surface markers involved in the fine tuning of TCR signaling-as potential prognostic biomarkers in resectable stages of non-small cel...

e21518 Background: Several platforms for non-invasive EGFR testing are currently used in the clinical setting, with sensitivities ranging from 30 to 100%. Comparison studies in prospective cohorts remain limited and reports evaluating mutant allelic fractions (MAFs) are particularly scarce. The RING observational trial (ClinicalTrials.gov identifie...

Precision medicine was born with the development of new diagnostic techniques and targeted drugs, yielding better outcomes in cancer care. With the evolution and increasing sensitivity for detecting oncogenic drivers, liquid biopsies (LBs), specifically cell-free DNA (cfDNA) analysis, have been proposed as a minimally-invasive technique for genomic...

Introduction: Among non-small cell lung cancer (NSCLC) patients, there is one molecularly defined subgroup harboring activating mutations in the epidermal growth factor receptor gene (EGFR), which results in constitutive activation of its intrinsic kinase activity. Consistent data have demonstrated that these patients have a better outcome when tre...

Relapse rates in surgically resected non-small-cell lung cancer (NSCLC) patients are between 30% and 45% within five years of diagnosis, which shows the clinical need to identify those patients at high risk of recurrence. The eighth TNM staging system recently refined the classification of NSCLC patients and their associated prognosis, but molecula...

Introduction/Background Lymphocytic infiltration areas (immunoreactive), frequently found in high-grade serous ovarian cancer (HGSOC), are associated with a better prognosis and increased survival. The cross-talk between tumour cells and lymphocytes conditions the capacity of the immune system (IS) to cope with the tumour in the so-called immune-ch...

Background: Recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) has a dismal prognosis with limited progression-free survival and overall survival, even when treated with different combinations of chemotherapy, targeted therapies and immunotherapy. We explored in vitro and in vivo the effect of the epidermal growth factor recept...

Finding novel targets in non-small cell lung cancer (NSCLC) is highly needed and identification of synthetic lethality between two genes is a new approach to target NSCLC. We previously found that TMPRSS4 promotes NSCLC growth and constitutes a prognostic biomarker. Here, through large-scale analyses across 5 public databases we identified consiste...

Background Non-small cell lung cancer (NSCLC) is the first cause of death cancer-related worldwide mainly due to high therapeutic resistance. This resistance is related to cancer stem-like cells (CSCs), for which the identification of targets and markers is still ongoing. Methods Primary cultures from 8 NSCLC patients were established as tumorsphe...

Background Cancer stem cells (CSCs) are targets poorly recognized by the immune surveillance system given that they induce an immunosuppressive microenvironment. The aim of this work is to study the interactions between CSCs and the immune microenvironment in NSCLC. Methods Tumor cells from 8 resected NSCLC patients and 12 cell lines were establis...

Background Lung cancer is the leading cause of cancer-related mortality worldwide. At diagnosis, 70% of patients present advanced disease being chemotherapy the standard of care. Although, specific tumour biomarkers that allow a better treatment selection and monitoring is absent at the moment. Enumeration and characterization of circulating tumor...

Background The microbiota community is considered as an organ of the human body. Recent studies have found that dysbiosis may have an impact on the interaction between immune regulation and tumor treatment. The main objective of this study is to characterize the gut microbiota in patients with non-small cell lung cancer (NSCLC) in advanced stages,...

Background Exosomes are small membranous vesicles (around 40-130 nm), that have been detected in different biological samples, that play a key role in NSCLC and being relevant in stem cell differentiation as well. The main objective of this study was to analyze the exosomes cargo from NSCLC cell cultures growth in monolayer (2D) and suspension cond...

Finding novel targets in NSCLC is highly needed and identification of synthetic lethality between two genes is a new approach to target NSCLC. TMPRSS4 is a serine protease that promotes NSCLC growth and that constitutes a prognosis biomarker. In this study we sought to identify synthetic lethal vulnerabilities of genes co-expressed with TMPRSS4. D...

The high resistance against current therapies found in non-small-cell lung cancer (NSCLC) has been associated to cancer stem-like cells (CSCs), a population for which the identification of targets and biomarkers is still under development. In this study, primary cultures from early-stage NSCLC patients were established, using sphere-forming assays...

e17526 Background: Recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) has a dismal prognosis with limited progression-free survival and overall survival, even when treated with different combinations of chemotherapy, targeted therapies and immunotherapy. We explored in vitro and in vivo the effect of the epidermal growth factor...

e20685 Background: Immunotherapy with anti-PD1/PDL1 monoclonal antibodies has become the second line standard treatment for most patients diagnosed of advanced Non-Small-Cell lung cancer (NSCLC). The aim of this study is to assess the utility of circulating biomarkers such as sPDL1, sPDL2, sCD137, sIDO, sTIM3, sCD28, sCD27, sCTLA4, sHVEM, sLAG3, sC...

Objectives: Resistance to tyrosine-kinase inhibitors (TKIs) is a clinical challenge in patients with oncogene-driven non-small-cell lung cancers (NSCLC). We have analyzed the utility of next-generation sequencing (NGS) of cell-free circulating tumor DNA (ctDNA) to impact the clinical care of patients with TKI resistance. Materials and methods: W...

Background: Approximately 30% of tumor biopsies from patients with advanced-stage lung adenocarcinomas yield insufficient tissue for successful molecular subtyping. We have analyzed the clinical utility of next-generation sequencing (NGS) of cell-free circulating tumor DNA (ctDNA) in patients with inadequate tumor samples for tissue genotyping. P...

Background: Liquid biopsy offers a minimally invasive alternative to tissue-based evaluation of mutational status in cancer. The goal of the present study was to evaluate the aggregate performance of OncoBEAM RAS mutation analysis in plasma of colorectal cancer (CRC) patients at 10 hospital laboratories in Spain where this technology is routinely...