A5044001263- Advanced Breast Cancer Therapies
- Cancer Genomics and Diagnostics
- Lung Cancer Research Studies
- HER2/EGFR in Cancer Research
- Cancer Cells and Metastasis
- Epigenetics and DNA Methylation
- Neuroendocrine Tumor Research Advances
- Cancer-related Molecular Pathways
- Single-cell and spatial transcriptomics
- Chronic Lymphocytic Leukemia Research
- Cancer Treatment and Pharmacology
- RNA modifications and cancer
- Pancreatic and Hepatic Oncology Research
- Metastasis and carcinoma case studies
- Lung Cancer Diagnosis and Treatment
- Microtubule and mitosis dynamics
- Cancer Research and Treatments
- Genetic factors in colorectal cancer
- PI3K/AKT/mTOR signaling in cancer
Hospital of Prato
2014-2024
Nuovo Ospedale di Prato
2020-2023
Azienda Usl Toscana Centro
2020-2022
Ospedale Misericordia e Dolce
2013
// Francesca De Luca 1, * , Giada Rotunno 2, Salvianti 3, Galardi 1 Marta Pestrin Stefano Gabellini Lisa Simi 3 Irene Mancini Alessandro Maria Vannucchi 2 Mario Pazzagli Angelo Di Leo Pamela Pinzani Sandro Pitigliani Medical Oncology Department, Hospital of Prato, Istituto Toscano Tumori, 59100, Italy Department Experimental and Clinical Medicine, University Florence, 50139, Clinical, Biomedical Sciences, These authors contributed equally to this work Correspondence to: Pinzani, email:...
Thymidine kinase 1 (TK1) is downstream to the CDK4/6 pathway, and TK activity (TKa) measured in blood a dynamic marker of outcome patients with advanced breast cancer (ABC). This study explores TK1 as biomarker palbociclib response, both vitro ABC.Modulation levels by were studied seven estrogen receptor-positive cell lines: sensitive (PDS) acquired resistance (PDR). TKa was assayed plasma obtained at baseline (T0), after one cycle (T1), disease progression on (T2) enrolled "To Reverse...
Within the OMITERC prospective study (OMIcs application from solid to liquid biopsy for a personalised ThERapy of Cancer), we explored prognostic role encompassing cell-free DNA (cfDNA) and circulating tumour cells (CTCs) in KRAS mutated metastatic colorectal cancer (mCRC). We defined workflow including pre-analytical analytical procedures collecting blood before therapy every 3 months until disease progression (PD). CTCs were counted by CellSearch® isolated DEPArray™. NGS sequencing cfDNA...
The aim of this study was to investigate if thymidine kinase-1 (TK1), a well-known proliferation marker, could represent valid circulating biomarker identify hormone receptor positive (HR+)/HER2 negative (HER2neg) metastatic breast cancer (MBC) patients most likely benefit from endocrine therapy (ET). We used the DiviTum™ assay analyze TK1 activity in cell lysates three HR+/HER2neg BC lines and plasma 31 MBC receiving ET. Blood samples were collected at treatment initiation, after one month...
Circulating tumor cells (CTCs) are prognostic in patients with advanced breast cancer (ABC). However, no data exist about their use treated palbociclib. We analyzed the role of CTC counts enrolled cTREnd study, a pre-planned translational sub-study TREnd (NCT02549430), that randomized ABC to palbociclib alone or plus endocrine therapy received prior line treatment. Moreover, we evaluated RB1 gene expression on CTCs and explored its within subpopulation. Forty-six ER-positive, HER2-negative...
Circulating tumor cell (CTC) count has prognostic significance in metastatic breast cancer, but the predictive utility of CTCs is uncertain. Molecular studies on have often been limited by a low number isolated from high background leukocytes. Improved enrichment techniques are now allowing molecular characterisation single CTCs, whereby markers may provide real-time assessment biomarker status blood test or "liquid biopsy", potentially negating need for more invasive tissue biopsy. The...
The purpose of the study was to explore feasibility a protocol for isolation and molecular characterization single circulating tumor cells (CTCs) from cancer patients using single-cell next generation sequencing (NGS) approach. To reach this goal we used as model an artificial sample obtained by spiking breast cell line (MDA-MB-231) into blood healthy donor. Tumor were enriched enumerated CellSearch(®) subsequently isolated DEPArray™ obtain or pooled pure samples be submitted analysis...
PURPOSE To identify prognostic circulating biomarkers to cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i), we performed a mutational analysis on tumor DNA (ctDNA) samples from patients included in the TREnd trial, which randomly assigned receive CDK4/6i palbociclib alone or with endocrine treatment (ET) they had progressed. METHODS Forty-six were enrolled this substudy. Plasma was collected before (T0), after first cycle of therapy (T1), at time progression (T2). ctDNA hybridization...
Abstract DNA-methylation alterations are common in cancer and display unique characteristics that make them ideal markers for tumor quantification classification. Here we present MIMESIS, a computational framework exploiting minimal signatures composed by few dozen informative sites to quantify classify signals tissue cell-free DNA samples. Extensive analyses of multiple independent heterogenous datasets including >7200 samples demonstrate the capability MIMESIS provide precise...
Non-invasive detection and quantification of circulating tumor DNA by DNAm signatures is emerging as powerful tool for monitoring disease status in pts with metastatic cancer. We recently developed MIMESIS, a computational workflow to design agnostic few dozen sites TC molecular subtype estimation liquid biopsy. Here we applied MIMESIS informed assay retrospective cohort mBC (MIMESIS-BC). 72 (42 ER+/HER2-, 2 ER+/HER2 N/A, 8 ER+/HER2+, 6 ER-/HER2+, 14 ER-/HER2-, up previous lines treatment)...
12031 Background: TK1 plays a critical role in DNA synthesis and cell proliferation. The DiviTum assay measures serum activity (sTKa), reflecting cancer Recent studies suggest this may provide real time prognostic information ABC. However, its HR+ ABC needs further validation. Methods: EFECT (n = 693) was double-blind, randomized trial of fulvestrant 250mg versus exemestane after progression on nonsteroidal aromatase inhibitor therapy for 58% pts had received > 1 prior ET sTKa...
Abstract Background: Little is known about the evolution of genetic aberrations during metastatic cancer progression and in response to systemic treatment. Obtaining repeated tissue biopsies often impractical. On other hand, it has been shown that circulating tumor cells (CTCs) can be easily followed disease course characterization at single cell level possible with high reliability [1]. Methods: Individual CTCs a ER+ HER2- de novo breast patient treated weekly paclitaxel/gemcitabine as...
Abstract Background: In the era of targeted therapies, chemotherapy (CT) is still a valuable treatment option for patients (pts) with HER2 negative metastatic breast cancer (MBC). The identification predictive and prognostic markers might improve response survival. Here we investigated role tumor subtypes, circulating cells (CTCs), mutations in genes or pathways interest, predicting to CT prognosis MBC pts within AARES trial. Methods: an open label multicentric randomised phase 2 trial...
Abstract 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 Rb protein resulting a decrease E2F activity and eventual cell cycle arrest. Thymidine kinase 1 well-known proliferation marker downstream pathway, whose can be measured plasma samples as readout tumor proliferation. Circulating thymidine (TKa) prognostic MBC patients (pts) treated ET,...
Abstract Introduction: Thymidine kinase is an established marker of cancer cell proliferation and its activity can be measured in blood. We others have recently shown that baseline dynamic evaluation circulating thymidine (TKa) during treatment gives prognostic predictive information patients with HR+, HER2-negative metastatic BC treated endocrine therapy alone, as well the setting CDK4/6 inhibition. However, there limited data regarding role TKa a biomarker operable BC. Here we present...
Abstract 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 clinical data recently indicated loss-of function mutations in RB1 increased expression CCNE1 biomarkers resistance a fraction breast cancer (BC) patients. In line with these studies, using panel resistant luminal BC lines made to we demonstrated common...