Francesco Bertoni

Francesco Bertoni
IOR Institute of Oncology Research · Lymphoma & Genomics Research Program

MD

About

692
Publications
55,132
Reads
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17,583
Citations
Introduction
Research topics: lymphoma genomics pre-clinical development of anti-lymphoma compounds molecular follow-up genomics in clinical trials MALT lymphoma Diffuse large B-cell lymphoma Marginal zone B-cell lymphoma Chronic lymphocytic leukemia
Additional affiliations
January 2000 - December 2012
Ente Ospedaliero Cantonale
Position
  • Oncology Institute of Southern Switzerland
January 1999 - present

Publications

Publications (692)
Article
Full-text available
Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid neoplasm in dogs and in humans. It is characterized by a remarkable degree of clinical heterogeneity that is not completely elucidated by molecular data. This poses a major barrier to understanding the disease and its response to therapy, or when treating dogs with DLBCL within clini...
Article
Background: Avanbulin (BAL27862) is a microtubule-targeting agent (MTA) that promotes tumor cell death by modulating the spindle assembly checkpoint. Preclinical studies in glioblastoma (GBM) have shown that avanbulin is also active in human cancer cells resistant to other MTAs used in the clinic. Lisavanbulin (BAL101553) is a water-soluble, oral,...
Article
Background: Diffuse large B cell lymphomas (DLBCLs) are aggressive tumors that account for almost half of all lymphoma incidences. In particular, double-hit and triple-hit DLBCLs, with translocations involving BCL2, MYC and/or BCL6, have a very poor prognosis and occur in up to 7% of cases. Double expressor DLBCLs, with overexpression of BCL2 and M...
Article
Background. Novel therapeutic targets are needed to improve the outcome of individuals with cancer. EG-011 is a small molecule with in vitro and in vivo anti-tumor activity in lymphoma and acute leukemias, but, at least so far, no activity in solid tumor models (Gaudio et al AACR 2019). Since no information was available on its target, we have now...
Article
Background: Lymphomas are characterized by aberrations in epigenetic proteins that contribute to establishing and maintaining the malignant phenotype. Gain of function mutations in EZH2 histone methyltransferase and inactivating mutations in CREBBP acetyltransferase occur in up to 30% of diffuse large B cell lymphomas (DLBCLs). Half of DLBCLs with...
Article
Background: The high variability in clinical responses observed in cancer patients highlights the need of a tailored therapeutic approach. A possible modality is to assess drugs sensitivity directly in the patients, by introducing small drug delivering devices in tumor sites for a very short period and then looking at the local anti-tumor effect. H...
Article
Background. G protein-coupled receptors (GPCRs) are integral membrane proteins that mediate cellular responses to endogenous (amines, cations, lipids, peptides, glycoproteins) and exogenous (light, tastants, odorants) stimuli. Altered signaling pathways associated with GPCRs are implicated in the pathophysiology of various diseases, such as CXCR3/4...
Article
PI3KPPinhibitors are active in patients with lymphoid neoplasms and a first series of them have been approved for the treatment of multiple types of B-cell lymphoid tumors, including marginal zone lymphoma (MZL). The identification of the mechanisms underlying either primary or secondary resistance is fundamental to optimize the use of novel drugs....
Chapter
Leukemias and lymphomas of B‐cell phenotype are relatively common in dogs, infrequent in cats, affect all breeds, ages, and sexes, and exhibit extraordinary biologic, morphologic, and clinical heterogeneity. This chapter describes the clinical and pathological features of veterinary B‐cell tumors and highlights the most significant differences and...
Article
Full-text available
Enhancer RNAs (eRNAs) are non-coding RNAs (ncRNAs) transcribed in enhancer regions. They play an important role in transcriptional regulation, mainly during cellular differentiation. eRNAs are tightly tissue- and cell-type specific and are induced by specific stimuli, activating promoters of target genes in turn. eRNAs usually have a very short hal...
Article
Full-text available
Aim: Bromodomain and extra-terminal domain (BET) proteins are epigenetic readers that play a fundamental role in transcription regulation. Preclinical and early clinical evidence sustain BET targeting as an anti-cancer approach. BET degraders are chimeric compounds comprising of a BET inhibitor, which allows the binding to BET bromodomains, linked...
Article
Full-text available
Background Diffuse large B-cell lymphoma (DLBCL) comprises at least two main biologically distinct entities: germinal center B-cell (GCB) and activated B-cell (ABC) subtype. Albeit sharing common lesions, GCB and ABC DLBCL present subtype-specific oncogenic pathway perturbations. ABC DLBCL is typically characterized by a constitutively active NF-kB...
Article
Full-text available
Promoter methylation represents one of the major epigenetic mechanisms responsible for the regulation of gene expression. Hypomethylating drugs are currently approved for the treatment of myelodysplastic syndromes and acute myeloid leukemia, and some studies have recently been carried out on diffuse large B cell lymphoma (DLBCL). DLBCL is a type of...
Preprint
During melanoma metastasization, tumor cells originated in the skin migrate via lymphatic vessels to the sentinel lymph node (sLN) in a process that facilitates their spread across the body. Here, we characterized the innate inflammatory responses to melanoma metastasis in the sLN. For this purpose, we confirmed the migration of fluorescent metasta...
Preprint
Full-text available
Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid neoplasm in dogs, being characterized by a remarkable degree of clinical heterogeneity not completely explained by molecular data. This poses a major barrier to understanding the disease and response to therapy or when using dogs with DLBCL in clinical trials. We performed an integra...
Article
This phase I trial evaluated the safety, tolerability, and preliminary activity of inotuzumab ozogamicin in combination with temsirolimus in patients with relapsed/refractory CD22 positive B-cell non-Hodgkin lymphomas. Nineteen patients received at least one dose of both study drugs. Dose-limiting toxicities consisted of thrombocytopenia, hypertrig...
Article
Because of its wide spectrum of targets and biological activities, the oxazole ring is a valuable heterocyclic scaffold in the design of new therapeutic agents with anticancer, antiviral, antibacterial, anti-inflammatory, neuroprotective, antidiabetic and antidepressant properties. The presence of two heteroatoms, oxygen and nitrogen, offers possib...
Article
Full-text available
Enhancers are regulatory regions of DNA, which play a key role in cell-type specific differentiation and development. Most active enhancers are transcribed into enhancer RNAs (eRNAs) that can regulate transcription of target genes by means of in cis as well as in trans action. eRNAs stabilize contacts between distal genomic regions and mediate the...
Article
Full-text available
Despite the development of new targeted and immune therapies, the prognosis of metastatic melanoma remains bleak. Therefore, it is critical to better understand the mechanisms controlling advanced melanoma to develop more effective treatment regimens. Hedgehog/GLI (HH/GLI) signaling inhibitors targeting the central pathway transducer Smoothened (SM...
Article
Full-text available
Histone deacetylase inhibitors (HDACis) are antitumor agents with distinct efficacy in hematologic tumors. Pracinostat is a pan-HDACi with promising early clinical activity. However, similar to other HDACis, its activity as a single agent is limited. Diffuse large B-cell lymphoma (DLBCL) includes distinct molecular subsets or metabolically defined...
Article
Full-text available
Abstract: EZH2 is an enzymatic subunit of PRC2, an epigenetic regulator that triggers the methylation of the histone H3 lysine 27 silencing the transcription of several genes. EZH2 has a critical role in cancer progression, since its overexpression has been associated with increased cancer cell invasiveness, drug resistance and poor patient sur-viv...
Article
Cancer is the dysregulated proliferation of cells caused by acquired mutations in key driver genes. The most frequently mutated driver genes promote tumorigenesis in various organisms, cell types, and genetic backgrounds. However, recent cancer genomics studies also point to the existence of context-dependent driver gene functions, where specific m...
Article
Full-text available
Stressful conditions induce the cell to save energy and activate a rescue program modulated by mammalian target of rapamycin (mTOR). Along with transcriptional and translational regulation, the cell relies also on post-transcriptional modulation to quickly adapt the translation of essential proteins. MicroRNAs play an important role in the regulati...
Article
Full-text available
Coastal countries have traditionally relied on the existing marine resources (e.g., fishing, food, transport, recreation, and tourism) as well as tried to support new economic endeavors (ocean energy, desalination for water supply, and seabed mining). Modern societies and lifestyle resulted in an increased demand for dietary diversity, better healt...
Article
Full-text available
Coastal countries have traditionally relied on the existing marine resources (e.g., fishing, food, transport, recreation, and tourism) as well as tried to support new economic endeavors (ocean energy, desalination for water supply, and seabed mining). Modern societies and lifestyle resulted in an increased demand for dietary diversity, better healt...
Article
Full-text available
Coastal countries have traditionally relied on the existing marine resources (e.g., fishing, food, transport, recreation, and tourism) as well as tried to support new economic endeavors (ocean energy, desalination for water supply, and seabed mining). Modern societies and lifestyle resulted in an increased demand for dietary diversity, better healt...
Article
Full-text available
In dogs, Burkitt-like lymphoma (B-LL) is rare tumour and it is classified as a high-grade B-cell malignancy. The diagnosis is challenging because of the similar histologic appearance with other histotypes, no defined phenotypical criteria and poorly described clinical aspects. The aim of the study was to provide a detailed description of clinical a...
Article
Full-text available
Driver genes with a mutually exclusive mutation pattern across tumor genomes are thought to have overlapping roles in tumorigenesis. In contrast, we show here that mutually exclusive prostate cancer driver alterations involving the ERG transcription factor and the ubiquitin ligase adaptor SPOP are synthetic sick. At the molecular level, the incompa...
Article
Ovarian cancer is the fifth cause of cancer-related deaths in women with high grade serous carcinoma (HGSOC) representing the most common histological subtype. Approximately 50% of HGSOC are characterized by deficiency in homologous recombination (HR), one of the main cellular pathways to repair DNA double strand breaks and one of the well-describe...
Article
Full-text available
The marine environment is a rich source of biologically active molecules for the treatment of human diseases, especially cancer. The adaptation to unique environmental conditions led marine organisms to evolve different pathways than their terrestrial counterparts, thus producing unique chemicals with a broad diversity and complexity. So far, more...
Article
Introduction. CD22 is a cell surface marker expressed by the vast majority of normal and neoplastic B-cells. ADCT-602 is an antibody drug conjugate (ADC) composed of Emab-C220, an engineered version of the anti-CD22 humanized IgG1 antibody epratuzumab, site-specifically conjugated to SG3249, which includes the DNA minor groove crosslinking pyrrolob...
Conference Paper
Introduction: Gains affecting chromosome 11 are recurrent events in lymphomas. The 11q24.3 gain occurs in 25% of diffuse large B-cell lymphoma (DLBCL), and it is associated with the overexpression of two ETS transcription factors, ETS1 and FLI1 (Blood 2013). Here, we have focused on the latter to identify the network of FLI1 regulated genes in GCB...
Article
Full-text available
Copy number aberrations (CNV/CNA) represent a major contribution to the somatic mutation landscapes in cancers, and their identification can lead to the discovery of oncogenetic targets as well as improved disease (sub-) classification. Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma in Western Countries and up to 40% of the affec...
Preprint
Full-text available
Background With the explosion of high-throughput data available in biology, the bottleneck is shifted to effective data interpretation. By taking advantage of the available data, it is possible to identify the biomarkers and signatures to distinguish subtypes of a specific cancer in the context of clinical trials. This requires sophisticated method...
Article
Full-text available
A new class of pyrrolo[2',3':3,4]cyclohepta[1,2-d][1,2]oxazoles was synthesized for the treatment of hyperproliferative pathologies, including neoplasms. The new compounds were screened in the 60 human cancer cell lines of the NCI drug screen and showed potent activity with GI50 values reaching the nanomolar level, with mean graph mid-points of 0.0...
Article
Bromodomain and extra-terminal domain (BET) proteins, cyclic adenosine monophosphate response element-binding protein (CBP), and the E1A-binding protein of p300 (EP300) are important players in histone acetylation. Preclinical evidence supports the notion that small molecules targeting these proteins individually or in combination can elicit antitu...
Article
Marginal zone lymphoma (MZL) represents a group of three distinct though overlapping lymphoid malignancies that includes extranodal, nodal and splenic marginal lymphoma. MZL patients usually present an indolent clinical course, although the disease remains largely incurable, save early stage disease that might be irradiated. Therapeutic advances ha...
Conference Paper
The PIM kinases are highly expressed in activated B-cell (ABC) diffuse large B-cell lymphoma (DLBCL). Oncogenic cooperation between PIMs and MYC has been demonstrated. Transgenic mice co-expressing Eμ-PIM and Eμ-MYC showed accelerated lymphomagenesis. Conversely, knockdown of PIMs dramatically decreased cMYC levels and lowered tumor incidence. Base...
Conference Paper
Background. DNA methyltransferases (DNMTs) are key enzymes necessary to the cells in order to establish and maintain methylation marks across the genome during both embrional development and adult cell divisions. DNMT1 is the main target of hypomethylating drugs 5-azacytidine (5-AZA) and 5-aza-2'-deoxycytidine (decitabine). These drugs have been us...
Conference Paper
Introduction. EUD-GK compounds, and in particular EUD-GK-91, show selectivity for a restricted number of kinases (ALK, RET, TRK, DDR2, ROS1) and have shown anti-tumor activity in specific solid tumor models (Zuccotto et al, EORTC-NCI-AACR 2016). Here, we have assessed a novel derivative of this class of compounds, EUD-GK-001, in a panel of lymphoma...
Article
Full-text available
The DNA damage response (DDR) is a well-coordinated cellular network activated by DNA damage. The unravelling of the key players in DDR, their specific inactivation in different tumor types and the synthesis of specific chemical inhibitors of DDR represent a new hot topic in cancer therapy. In this article, we will review the importance of DDR in l...
Article
Full-text available
Diffuse large B cell lymphoma (DLBCL) is a heterogenous disease that has been distinguished into at least two major molecular entities, the germinal center-like B cell (GCB) DLBCL and activated-like B cell (ABC) DLBCL, based on transcriptome expression profiling. A recurrent ch11q24.3 gain is observed in roughly a fourth of DLBCL cases resulting in...
Preprint
Full-text available
Driver genes with a mutually exclusive mutation pattern across tumor genomes are thought to have overlapping roles in tumorigenesis. In contrast, we show here that mutually-exclusive prostate cancer driver alterations involving the ERG transcription factor and the ubiquitin ligase adaptor SPOP are synthetic sick. At the molecular level, the incompa...
Article
The Bromo- and Extra-Terminal domain (BET) family proteins act as “readers” of acetylated histones and they are important transcription regulators. BRD2, BRD3, BRD4 and BRDT, part of the BET family, are important in different tumors, where upregulation or translocation often occurs. The potential of targeting BET proteins as anti-cancer treatment o...
Article
There are three different marginal zone lymphoma (MZLs) entities: the extranodal MZL of mucosa- associated lymphoid tissue, the splenic MZL, and the nodal MZL. The 3 MZLs share common lesions (trisomies of chromosomes 3 and 18, deletions at 6q23), and alterations of the nuclear factor κB pathway are frequent events in all of them, but they also dif...
Article
The X-ray structure of the catalytic domain of the EphA3 tyrosine kinase in complex with a previously reported type II inhibitor was used to design two novel quinoxaline derivatives, inspired by kinase inhibitors that have reached clinical development. These two new compounds were characterized by an array of cell-based assays and gene expression p...
Article
Full-text available
Marine organisms produce a vast diversity of metabolites with biological activities useful for humans, e.g. cytotoxic, antioxidant, anti-microbial, insecticidal, herbicidal, anticancer, pro-osteogenic and pro-regenerative, analgesic, anti-inflammatory, anti-coagulant, cholesterol-lowering, nutritional, photoprotective, horticultural or other benefi...
Article
Full-text available
We have recently identified and characterized two pseudogenes (HMGA1P6 and HMGA1P7) of the HMGA1 gene, which has a critical role in malignant cell transformation and cancer progression. HMGA1P6 and HMGAP17 act as microRNA decoy for HMGA1 and other cancer-related genes upregulating their protein levels. We have previously shown that they are upregul...
Article
Anti-tubulin agents constitute a large class of compounds with broad activity both in solid tumors and hematologic malignancies, due to the interference with microtubule dynamics. Since microtubules play crucial roles in the regulation of the mitotic spindles, the interference with their function usually leads to a block in cell division with arres...