A5065746326- Colorectal Cancer Treatments and Studies
- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
- Cancer Immunotherapy and Biomarkers
- Lung Cancer Treatments and Mutations
- Cancer Treatment and Pharmacology
- Gastric Cancer Management and Outcomes
- HER2/EGFR in Cancer Research
- Advanced Breast Cancer Therapies
- Lung Cancer Research Studies
- Colorectal and Anal Carcinomas
- Hepatocellular Carcinoma Treatment and Prognosis
- Radiomics and Machine Learning in Medical Imaging
- Pancreatic and Hepatic Oncology Research
- Management of metastatic bone disease
- Colorectal Cancer Surgical Treatments
- Metabolism, Diabetes, and Cancer
- Ovarian cancer diagnosis and treatment
- Intraperitoneal and Appendiceal Malignancies
- PI3K/AKT/mTOR signaling in cancer
- Glioma Diagnosis and Treatment
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Neuroendocrine Tumor Research Advances
- Cancer therapeutics and mechanisms
Fondazione IRCCS Istituto Nazionale dei Tumori
2017-2024
Tumori Foundation
2022
University of Milan
2021
University of Padua
2016-2020
Istituti di Ricovero e Cura a Carattere Scientifico
2015-2019
Agostino Gemelli University Polyclinic
2019
Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
2019
Candiolo Cancer Institute
2019
University of Turin
2019
Istituto Oncologico Veneto
2014-2016
Several post hoc analyses of randomized controlled trials (RCTs) suggested the importance microsatellite instability (MSI) as a positive predictive factor to immunotherapy in patients with advanced gastric cancer (GC); however, individually these have low statistical power.RCTs investigating treatment or without an anti-programmed cell death protein 1 (PD-1) agent for GC and providing outcome according MSI status were selected. The hazard ratio (HR) odds used compare effect on survival...
Abstract Anti-BRAF/EGFR therapy was recently approved for the treatment of metastatic BRAF V600E colorectal cancer (mCRC BRAF-V600E ). However, a large fraction patients do not respond, underscoring need to identify molecular determinants response. Using whole-exome sequencing in discovery cohort with mCRC treated anti-BRAF/EGFR therapy, we found that inactivating mutations RNF43 , negative regulator WNT, predict improved response rates and survival outcomes microsatellite-stable (MSS)...
This is a multicenter, single-arm phase II trial evaluating the efficacy and safety of an immune-sensitizing strategy with temozolomide priming followed by combination low-dose ipilimumab nivolumab in patients microsatellite-stable (MSS) O6-methylguanine-DNA methyltransferase (MGMT)-silenced metastatic colorectal cancer (mCRC).Patients pretreated mCRC were centrally prescreened for MSS status MGMT silencing (ie, lack expression immunohistochemistry plus methylation pyrosequencing). Eligible...
Despite unprecedented benefit from immune checkpoint inhibitors (ICIs) in patients with mismatch repair deficient (dMMR)/microsatellite instability high (MSI-H) advanced gastrointestinal cancers, a relevant proportion of shows primary resistance or short-term disease control. Since malignant effusions represent an immune-suppressed niche, we investigated whether peritoneal involvement without ascites is poor prognostic factor dMMR/MSI-H metastatic colorectal cancer (mCRC) and gastric (mGC)...
358 Background: In resectable GAC/GEJAC, MSI status is associated with better survival and potential lack of benefit from chemotherapy. Given the high responsiveness tumors to immunotherapy, neoadjuvant or definitive dual CTLA-4/PD(L)-1 inhibition may allow omission chemotherapy surgery. Methods: INFINITY a multicentre, single-arm, multi-cohort phase II trial (NCT04817826) investigating activity safety tremelimumab+durvalumab as (Cohort 1) 2) treatment for MSI, mismatch repair deficient...
To verify whether the intensification of upfront chemotherapy backbone with a modified schedule fluorouracil, leucovorin, oxaliplatin, and irinotecan (mFOLFOXIRI) increases activity oxaliplatin when both regimens are combined panitumumab as initial treatment for RAS BRAF wild-type (wt) metastatic colorectal cancer (mCRC).TRIPLETE was prospective, open-label, phase III trial in which previously untreated patients unresectable wt mCRC were randomly assigned 1:1 to FOLFOX/panitumumab (control...
POLE and POLD1 proofreading deficiency (POLE/D1pd) define a rare subtype of ultramutated metastatic colorectal cancer (mCRC; over 100 mut/Mb). Disease-specific data about the activity efficacy immune checkpoint inhibitors (ICIs) in POLE/D1pd mCRC are lacking it is unknown whether outcomes may be different from mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) mCRCs treated with ICIs.
Background: Beyond programmed death ligand 1 (PD-L1), no other biomarkers for immunotherapy are used in daily practice. We previously created EPSILoN (Eastern Cooperative Oncology Group performance status (ECOG PS), smoking, liver metastases, lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR)) score, a clinical/biochemical prognostic 154 patients treated with second/further-line immunotherapy. This study’s aim was to validate score different population group. Methods: 193 were...
Abstract Tumors bearing homologous recombination deficiency are extremely sensitive to DNA double strand breaks induced by several chemotherapeutic agents. ATM gene, encoding a protein involved in damage response, is frequently mutated colorectal cancer (CRC), but its potential role as predictive and prognostic biomarker has not been fully investigated. We carried out multicenter effort aimed at defining the impact of mutational status metastatic CRC (mCRC) patients. Mutational profiles were...
Background Obesity is a risk factor for malignancy; however, its prognostic role in patients with metastatic melanoma controversial. We aim to investigate the of body mass index (BMI) receiving mitogen-activated pathway kinase inhibitors (MAPKi), immune checkpoint (ICIs) alone or their sequence. Methods Data on ≥1 line systemic treatment were retrieved from prospectively collected databases. Progression-free survival (PFS) and overall (OS) analyzed by means multivariable stratified Cox...
3511 Background: Preop CTRT is considered the standard of care in management LARC. RT can induce antigen release from a low neoantigen-burden tumor (such as mismatch repair proficient colorectal cancer) and activate dendritic cells leading to CD8+ T lymphocyte-mediated anticancer immune response. In LARC patients, neoadjuvant increases PD-L1 expression cells, strongly suggesting combinatory strategy with PD-1/PD-L1 pathway blockade. Based on such considerations, we have designed AVANA study...
Myeloid-derived suppressor cells (MDSC) are well-known key negative regulators of the immune response during tumor growth, however scattered is knowledge their capacity to influence and adapt different microenvironments markers that identify those capacities. Here we show secreted protein acidic rich in cysteine (SPARC) identifies both human mouse MDSC with suppressive pro-tumoral activities including induction epithelial-to-mesenchymal transition (EMT) angiogenesis. In mice genetic deletion...
Few real-world series on the efficacy and safety of anti-programmed cell death protein-1(PD-1)/programmed ligand-1(PD-L1)-based therapy are available in molecularly unselected patients with poor performance status (PS) specific types advanced cancers, because such populations typically excluded from clinical trials due to life expectancy risk toxicity.This multicenter retrospective case included microsatellite instability (MSI)-high metastatic cancers Eastern Cooperative Oncology Group...
LBA4002 Background: In pts with HER2-negative advanced gastric/GEJ cancer and PD-L1 low/absent expression, platinum/fluoropyrimidine doublets are a standard first-line therapy. this patient population, the outcomes unsatisfactory second-line therapy is given in only 40% of clinical trial patients. Switch consolidation maintenance may prolong benefit initial strategy delay deterioration. Despite ramucirumab failing to both progression-free survival (PFS) overall (OS) setting, paclitaxel plus...
Several uncommon genomic alterations beyond RAS and BRAFV600E mutations drive primary resistance to anti-epidermal growth factor receptors (EGFRs) in metastatic colorectal cancer (mCRC). Our PRESSING panel (including PIK3CA exon 20/AKT1/PTEN mutations, ERBB2/MET amplifications, gene fusions, microsatellite instability-high status) represented a paradigm of negative hyperselection with more precise tailoring EGFR blockade. However, modest proportion hyperselected mCRC has intrinsic...
In GI cancers, anaplastic lymphoma kinase (ALK) rearrangements are extremely less frequent than in non-small-cell lung cancer but may be important to offer personalized strategies of treatment selected patients. Data about the activity and efficacy ALK inhibitors (ALKi) cancers scarce.We assembled a clinical molecular international data set pretreated patients with metastatic or nonresectable primary tumor origin documented rearrangement treated at least one line ALKi. Measurable disease as...
Abstract Gene expression signatures (“molecular phenotypes”) are extensively utilized in cancer research. Using direct capture Perturb-seq (dcPerturb-seq), we surveyed how molecular phenotypes gastric (GC) shaped by cell-intrinsic genetic alterations interacting with cell-extrinsic therapeutic exposures. Interrogating >200 GC-related genes against 4 distinct epigenetic drug classes across multiple lines, captured 18.9 million pharmacogenomic interactions 669,065 cells representing...