Matteo Benelli

Matteo Benelli
Azienda USL Toscana Centro, Prato, Italy · Hospital of Prato

PhD
Cancer genomics, epigenetics and radiomics. Pre and post-doctoral positions available in my lab. DM me if interested.

About

162
Publications
18,068
Reads
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4,591
Citations
Additional affiliations
February 2015 - October 2016
Università degli Studi di Trento
Position
  • PostDoc Position
February 2012 - February 2015
Azienda Ospedaliero Universitaria Careggi
Position
  • Principal Bioinformatician
January 2009 - January 2012
University of Florence
Position
  • PhD Student
Education
February 2008 - March 2012
University of Florence
Field of study
  • Non Linear Dynamics and Complex Systems
September 2006 - April 2008
University of Florence
Field of study
  • Nuclear and Sub-Nuclear Physics
September 2002 - December 2006
University of Florence
Field of study
  • Physics

Publications

Publications (162)
Article
1012 Background: Independent early dynamic assessment (baseline [D0] and day 15 of first cycle [D15]) of both TKa and ctDNA was prognostic and predictive in pts with HR+, HER2− ABC treated with RIB+LET enrolled in the BioItaLEE trial (NCT03439046). Here we performed a combined analysis of these two biomarkers. Methods: 287 pts were enrolled in the...
Article
Background Biomarkers for cyclin-dependent kinase 4/6 inhibitors, such as palbociclib, for patients with hormone receptor-positive/HER2-negative metastatic breast cancer are lacking. Thymidine kinase is a proliferation marker downstream of the cyclin-dependent kinase 4/6 pathway. We prospectively investigated the prognostic role of serum thymidine...
Article
Background: ctDNA analysis is emerging as an attractive non-invasive approach to characterize tumor biology, describe its evolution over time, and predict treatment benefit. Here, we assessed the prognostic and predictive role of baseline and dynamic ctDNA analysis in HR+/HER2- aBC patients (pts) treated with R+L. Methods: 287 postmenopausal pts we...
Article
Full-text available
We aim to elucidate the prognostic value of PIK3CA mutations and copy number (CN) gain (PIK3CA-mut/gain) in hormone receptor-positive and HER2-negative (HR + /HER2−) breast cancer (BC). We analyzed primary HR + /HER2− BC from three publicly available datasets comprising over 2000 samples and assessed the associations with tumoral and clinical chara...
Article
Full-text available
Background: Colorectal cancer (CRC) is the fourth most commonly diagnosed and third most deadly cancer worldwide. Surgery is the main treatment option for early disease; however, a relevant proportion of CRC patients relapse. Here, variations among preoperative and postoperative serum metabolomic fingerprint of CRC patients were studied, and possib...
Article
Full-text available
Differentially DNA methylated regions (DMRs) inform on the role of epigenetic changes in cancer. We present Rocker-meth, a new computational method exploiting a heterogeneous hidden Markov model to detect DMRs across multiple experimental platforms. Through an extensive comparative study, we first demonstrate Rocker-meth excellent performance on sy...
Article
Full-text available
Pan-cancer studies sketched the genomic landscape of the tumor types spectrum. We delineated the purity- and ploidy-adjusted allele-specific profiles of 4,950 patients across 27 tumor types from the Cancer Genome Atlas (TCGA). Leveraging allele-specific data, we reclassified as loss of heterozygosity (LOH) 9% and 7% of apparent copy-number wild-typ...
Article
Full-text available
Triage is crucial for patient’s management and estimation of the required intensive care unit (ICU) beds is fundamental for health systems during the COVID-19 pandemic. We assessed whether chest computed tomography (CT) of COVID-19 pneumonia has an incremental role in predicting patient’s admission to ICU. We performed volumetric and texture analys...
Article
Full-text available
AURORA aims to study the processes of relapse in metastatic breast cancer (MBC) by performing multi-omics profiling on paired primary tumors and early-course metastases. Among 381 patients (primary tumor and metastasis pairs: 252 targeted gene sequencing, 152 RNA sequencing, 67 single nucleotide polymorphism arrays), we found a driver role for GATA...
Article
Full-text available
CDK4/6 inhibitors (CDK4/6i) and endocrine therapy are the standard treatment for patients with hormone receptor-positive and HER2 negative (HR+/HER2−) metastatic breast cancer. Patients might show intrinsic and acquired resistance, which leads to treatment failure and progression. Circulating biomarkers have the potential advantages of recognizing...
Article
Purpose The purpose of this multicenter phantom study was to exploit an innovative approach, based on an extensive acquisition protocol and unsupervised clustering analysis, in order to assess any potential bias in apparent diffusion coefficient (ADC) estimation due to different scanner characteristics. Moreover, we aimed at assessing, for the firs...
Article
Full-text available
Background Circulating tumor cells (CTCs) are prognostic in patients with advanced breast cancer (ABC). However, no data exist about their use in patients treated with palbociclib. We analyzed the prognostic role of CTC counts in patients enrolled in the cTREnd study, a pre-planned translational sub-study of TREnd (NCT02549430), that randomized pat...
Conference Paper
Background: The CDK4/6 inhibitor palbociclib (P) plus fulvestrant (F) is approved for the treatment of patients (pts) with luminal metastatic breast cancer (MBC) progressed on prior endocrine therapy (ET). Despite clinical activity, a significant proportion of pts in this setting show primary resistance to P+F, with treatment failure within 3-6 mon...
Article
Full-text available
Purpose: CDK4/6 inhibitors are highly effective against ER+/HER2- breast cancer (BC); however, intrinsic and acquired resistance is common. Elucidating the molecular features of sensitivity and resistance to CDK4/6i's may lead to identification of predictive biomarkers and novel therapeutic targets, paving the way toward improving patient outcomes...
Preprint
Full-text available
Rationale. Triage is crucial for patient's management and estimation of the required Intensive Care Unit (ICU) beds is fundamental for Health Systems during the COVID-19 pandemic. Objective. To assess whether chest Computed Tomography (CT) of COVID-19 pneumonia has an incremental role in predicting patient's admission to ICU. Methods. We performed...
Article
Full-text available
Liquid biopsy based on cell-free DNA (cfDNA) enables non-invasive dynamic assessment of disease status in patients with cancer, both in the early and advanced settings. The analysis of DNA-methylation (DNAm) from cfDNA samples holds great promise due to the intrinsic characteristics of DNAm being more prevalent, pervasive, and cell- and tumor-type...
Article
CDK4/6 inhibitors (CDK4/6i) in combination with endocrine therapy are the mainstay of treatment for patients with hormone receptor-positive, HER2 negative (HR+/HER2neg) metastatic breast cancer. However, resistance - either de novo or acquired - invariably occurs, leading to treatment failure and cancer progression. Genomic alterations, gene expres...
Article
Full-text available
In the treatment of advanced non-small cell lung cancer (NSCLC), immune checkpoint inhibitors have shown remarkable results. However, not all patients with NSCLC respond to this drug treatment or receive durable benefits. Thus, patient stratification and selection, as well as the identification of predictive biomarkers, represent pivotal aspects to...
Article
Full-text available
Advanced prostate cancer initially responds to hormonal treatment, but ultimately becomes resistant and requires more potent therapies. One mechanism of resistance observed in around 10–20% of these patients is lineage plasticity, which manifests in a partial or complete small cell or neuroendocrine prostate cancer (NEPC) phenotype. Here, we invest...
Preprint
Full-text available
Differentially DNA methylated regions (DMRs) inform on the role of epigenetic changes in cancer. We present Rocker-meth, a computational method exploiting a heterogeneous hidden Markov model to detect DMRs across multiple experimental platforms. Its application to more than 6,000 methylation profiles across 14 tumor types provides a comprehensive c...
Article
Full-text available
TNFα is the main proinflammatory cytokine implicated in the pathogenesis of neurodegenerative disorders, but it also modulates physiological functions in both the developing and adult brain. In this study, we investigated a potential direct role of TNFα in determining phenotypic changes of a recently established cellular model of human basal forebr...
Conference Paper
p>Introduction Gene fusions (GFs) are genomic alterations with oncogenic potential. This class of alterations is highly actionable with targeted therapies showing high rates of durable responses in agnostic settings such as tumors with NTR K fusions. Recurrent GFs are rare in metastatic breast cancer (mBC) and ESR1 fusions drive endocrine resistan...
Article
Full-text available
The authors would like to apologise for an error in the annotation of one of the STAG3 variants in the text, Figure 2 and Supplementary Table SV of the above manuscript. The variant NM_001282718:c.1759dupG should be NM_001282718.2:c. 1762dupG:p.(Ala588GlyfsTer9); referring to the largest transcript the variant is equivalent to NM_012447.3:c.1936dup...
Article
Quantitative analysis of biomedical images, referred to as radiomics, is emerging as a promising approach to facilitate clinical decisions and improve patient stratification. The typical radiomic workflow includes image acquisition, segmentation, feature extraction, and analysis of high-dimensional datasets. While procedures for primary radiomic an...
Preprint
Disruptive mutations in the chromodomain helicase DNA binding protein 8 ( CHD8 ) have been recurrently associated with Autism Spectrum Disorders (ASD). In normal cellular physiology, CHD8 co-purifies with MLL1 and MOF transcriptional activation complex, with elongating RNAPII and directly binds to DNA promoters and enhancers regions, thus a regulat...
Article
Disruptive mutations in the chromodomain helicase DNA binding protein 8 (CHD8) have been recurrently associated with Autism Spectrum Disorders (ASD). In normal cellular physiology, CHD8 co-purifies with MLL1 and MOF transcriptional activation complex, with elongating RNAPII and directly binds to DNA promoters and enhancers regions, thus a regulator...
Article
Full-text available
The majority of breast cancers express the estrogen receptor (ER) and are dependent on estrogen for their growth and survival. Endocrine therapy (ET) is the standard of care for these tumors. However, a superior outcome is achieved in a subset of ER positive (ER+)/human epidermal growth factor receptor 2 negative (HER2−) metastatic breast cancer pa...
Article
Full-text available
Tumor DNA circulates in the plasma of cancer patients admixed with DNA from noncancerous cells. The genomic landscape of plasma DNA has been characterized in metastatic castration-resistant prostate cancer (mCRPC) but the plasma methylome has not been extensively explored. Here, we performed next-generation sequencing (NGS) on plasma DNA with and w...
Preprint
Full-text available
Advanced prostate cancer initially responds to hormonal treatment, but ultimately becomes resistant and requires more potent therapies. One mechanism of resistance observed in ~10% of these patients is through lineage plasticity, which manifests in a partial or complete small cell or neuroendocrine prostate cancer (NEPC) phenotype. Here, we investi...
Article
Full-text available
Loss of androgen receptor (AR) signaling dependence occurs in approximately 15%-20% of advanced treatment-resistant prostate cancers, and this may manifest clinically as transformation from a prostate adenocarcinoma histology to a castration-resistant neuroendocrine prostate cancer (CRPC-NE). The diagnosis of CRPC-NE currently relies on a metastati...
Article
8 Background: Loss of androgen receptor signaling dependence occurs in approximately 20% of treatment resistant prostate cancers, and this may manifest as transformation to castration resistant neuroendocrine prostate cancer (CRPC-NE). The diagnosis of CRPC-NE relies on a metastatic tumor biopsy, which is invasive for patients. Here we study ctDNA...
Conference Paper
Introduction: CDK4/6 inhibitors, such as palbociclib, target the cyclin-dependent kinases 4 and 6, essential for cell cycle regulation. Preclinical studies have suggested potential determinants of palbociclib sensitivity and clinical data have recently indicated loss-of function mutations in RB1 and increased expression of CCNE1 as potential biomar...
Conference Paper
Introduction: Thymidine kinase is an established marker of cancer cell proliferation and its activity can be measured in blood. We and others have recently shown that baseline and dynamic evaluation of circulating thymidine kinase activity (TKa) during treatment gives prognostic and predictive information in patients with HR+, HER2-negative metasta...
Conference Paper
Background: The CDK4/6 inhibitors (i) palbociclib (Palbo), ribociclib, and abemaciclib remarkably improved the outcome of patients with metastatic ER+/HER2- breast cancer (BC) and are now under clinical investigation in early BC. Despite high efficacy, and acquired resistance to CDK4/6i is common. Elucidating the molecular basis for sensitivity and...
Article
Purpose: Thymidine kinase 1 (TK1) is downstream to the CDK4/6 pathway, and TK activity (TKa) measured in blood is a dynamic marker of outcome in patients with advanced breast cancer (ABC). This study explores TK1 as a biomarker of palbociclib response, both in vitro and in patients with ABC. Experimental design: Modulation of TK1 levels and acti...
Article
Full-text available
Background Chemotherapy added to anti-HER2 agents (H) is the treatment of choice in patients with HER2+ early breast cancer. However, HER2+ tumours are clinically and biologically heterogeneous, and treatment response varies significantly by hormone receptor (HR) status and molecular subtype. Predictive biomarkers are needed in this context. This s...
Article
Temozolomide is an oral alkylating agent used for treating several cancers including glioblastoma and melanoma. Promising, albeit limited, activity and efficacy of temozolomide have been reported in pretreated patients with metastatic colorectal cancer bearing MGMT promoter methylation. MGMT silencing and proficiency of the mismatch repair system w...
Article
Gene-expression assays were originally validated retrospectively as tools of prognostication, with evidence emerging from more recent prospectively-conducted studies such as MINDACT and TAILORx supporting their clinical validity and utility as biomarkers in identifying patients with luminal breast cancer who might be spared chemotherapy. However, t...
Article
Full-text available
The recent arrival of CDK4/6 inhibitor agents, with an approximate doubling of progression-free survival (PFS) associated with their use in hormone receptor-positive, HER2-negative advanced breast cancer (BC), has radically changed the approach to managing this disease. However, resistance to CDK4/6 inhibitors is considered a near-inevitability in...
Conference Paper
Background: The CDK4/6 inhibitor palbociclib (P) is approved for the treatment of luminal metastatic breast cancer (MBC) in combination with endocrine therapy (ET). It leads to reduced phosphorylation of the Rb protein resulting in a decrease in E2F activity and eventual cell cycle arrest. Thymidine kinase 1 is a well-known cancer proliferation mar...
Conference Paper
Background: The CDK4/6 inhibitor palbociclib (P) is approved for the treatment of luminal metastatic breast cancer (MBC) in combination with endocrine therapy (ET). It leads to reduced phosphorylation of the Rb protein resulting in a decrease in E2F activity and eventual cell cycle arrest. Thymidine kinase 1 is a well-known cancer proliferation mar...
Conference Paper
CDK4/6 inhibitors, such as palbociclib, target the cyclin-dependent kinases 4 and 6, essential for cell cycle regulation. CDK4/6 inhibitors are established treatment options in patients with endocrine receptor positive, HER2 negative metastatic breast cancer (BC). We recently conducted a transcriptomic study of seven palbociclib resistant luminal B...
Conference Paper
DNA methylation (DNAm) is an essential player of gene regulation and therefore one of the most studied epigenetic mechanisms. Alterations of DNAm have been associated with a wide range of diseases, including cancer. Most studies on DNAm focused on the characterization of methylation sites, despite the recognition that DNAm changes spanning entire g...
Article
BACKGROUND: Thymidine kinase 1 (TK1) plays a critical role in DNA synthesis and cell proliferation. Recent studies have shown potential for serum TK1 activity (sTKa) as a prognostic marker and indicator of early response to endocrine therapy in advanced breast cancer. The aim of this study is to assess the correlation between sTKa and patient outco...
Article
Full-text available
Abstract Currently, there is limited data regarding the effectiveness of standard subsequent line therapies such as endocrine therapy, chemotherapy, or targeted agents after progression on CDK4/6 inhibitor-based regimens. This paper describes time-to-treatment failure beyond progression on palbociclib or palbociclib+endocrine therapy in patients en...
Article
Study question: What is the diagnostic potential of next generation sequencing (NGS) based on a 'mouse azoospermia' gene panel in human non-obstructive azoospermia (NOA)? Summary answer: The diagnostic performance of sequencing a gene panel based on genes associated with mouse azoospermia was relatively successful in idiopathic NOA patients and...
Article
Full-text available
Heterogeneity in the genomic landscape of metastatic prostate cancer has become apparent through several comprehensive profiling efforts, but little is known about the impact of this heterogeneity on clinical outcome. Here, we report comprehensive genomic and transcriptomic analysis of 429 patients with metastatic castration-resistant prostate canc...
Article
Full-text available
Objective Primary tumour location is regarded as a reliable surrogate of colorectal cancer biology. Sensitivity to anti-EGFRs (Epidermal Growth Factor Receptor) of metastatic transverse colon cancers (mTCCs) has usually been assumed similar to right-sided tumours; however, evidence about the clinical behaviour of mTCC is limited. Thus, to verify se...
Article
Background: Despite the efficacy of the combinations of endocrine therapy (ET) and CDK4/6 inhibitors in the hormone receptor positive (HR+) metastatic breast cancer (BC) setting, the majority of patients eventually acquire resistance to these treatments. The loss of Rb activity is an important mechanism of acquired resistance to CDK4/6 inhibitors....