A5062479121- Advanced Breast Cancer Therapies
- Cancer Immunotherapy and Biomarkers
- Lung Cancer Treatments and Mutations
- Fibroblast Growth Factor Research
- Cancer Genomics and Diagnostics
- HER2/EGFR in Cancer Research
- Myasthenia Gravis and Thymoma
- Cancer-related Molecular Pathways
- PI3K/AKT/mTOR signaling in cancer
- Neuroendocrine Tumor Research Advances
- Colorectal Cancer Treatments and Studies
- Renal cell carcinoma treatment
- Epigenetics and DNA Methylation
- Lung Cancer Research Studies
- Pancreatic and Hepatic Oncology Research
- Lung Cancer Diagnosis and Treatment
- Hedgehog Signaling Pathway Studies
- Monoclonal and Polyclonal Antibodies Research
- Economic and Financial Impacts of Cancer
- Cancer-related gene regulation
- Metastasis and carcinoma case studies
- Kruppel-like factors research
- Breast Cancer Treatment Studies
- Prostate Cancer Treatment and Research
- Cutaneous Melanoma Detection and Management
University of Naples Federico II
2016-2025
Southwestern Medical Center
2019-2024
The University of Texas Southwestern Medical Center
2019-2024
Federico II University Hospital
2024
Harold C. Simmons Comprehensive Cancer Center
2019-2021
Vanderbilt University Medical Center
2018
Abstract Using an ORF kinome screen in MCF-7 cells treated with the CDK4/6 inhibitor ribociclib plus fulvestrant, we identified FGFR1 as a mechanism of drug resistance. FGFR1-amplified/ER+ breast cancer and transduced were resistant to fulvestrant ± or palbociclib. This resistance was abrogated by treatment FGFR tyrosine kinase (TKI) lucitanib. Addition TKI erdafitinib palbociclib/fulvestrant induced complete responses patient-derived-xenografts. Next generation sequencing circulating tumor...
Abstract CDK4/6 inhibitors (CDK4/6i) have improved survival of patients with estrogen receptor-positive (ER+) breast cancer. However, treated CDK4/6i eventually develop drug resistance and progress. RB1 loss-of-function alterations confer to CDK4/6i, but the optimal therapy for these is unclear. Through a genome-wide CRISPR screen, we identify protein arginine methyltransferase 5 (PRMT5) as molecular vulnerability in ER+/ -knockout cancer cells. Inhibition PRMT5 blocks G1-to-S transition...
Several evidences suggest a marked angiogenic dependency in triple-negative breast cancer (TNBC) tumorigenesis and potential sensitivity to anti-angiogenic agents. Herein, the putative role of Hedgehog (Hh) pathway regulating TNBC-dependent angiogenesis was investigated.Expression regulation Hh transcription factor glioma-associated oncogene homolog1 protein (GLI1) were studied on endothelial compartment TNBC-initiated angiogenesis. To evaluate translational relevance our findings,...
In patients with ER+ metastatic breast cancer (mBC), the first-line treatment involves combination of endocrine therapy (ET) and CDK4/6 inhibitors (CDK4/6i). However, a significant group experiences disease progression, emphasizing urgent clinical need to identify novel anti-tumor therapies. We previously generated cells resistant fulvestrant (ER downregulator) abemaciclib (CDK4/6 inhibitor) from MCF7 T47D (MCF7-FAR T47D-FAR). RNA-seq-based Gene Set Enrichment Analysis (GSEA) revealed...
Anti-programmed cell death 1 (PD1) is the first-choice treatment in patients with advanced cutaneous squamous carcinoma (cSCC), when curative options are unavailable. However, reliable biomarkers for patient selection still lacking. In this translational study, clinical annotations, tissue and liquid biopsies were acquired to investigate association between sustained objective responses transcriptional profiles, immune dynamics tumor peripheral blood samples, as well circulating cytokine...
Cetuximab is the only targeted agent approved for treatment of head and neck squamous cell carcinomas (HNSCC), but low response rates disease progression are frequently reported. As phosphoinositide 3-kinase (PI3K) mammalian target rapamycin (mTOR) pathways have an important role in pathogenesis HNSCC, we investigated their involvement cetuximab resistance. Different human cancer lines sensitive or resistant to were tested dual PI3K/mTOR inhibitor PF-05212384 (PKI-587), alone combination,...
The urokinase-type plasminogen activator receptor (uPAR) is a GPI-anchored cell membrane that focuses urokinase (uPA) proteolytic activity on the surface. Its expression increased in many human cancers, including non-small lung cancer (NSCLC) and colorectal (CRC), correlates with poor prognosis early invasion metastasis. uPAR able to control, through cross-talk tyrosine kinase receptors, shift between tumor dormancy proliferation, usually precedes metastasis formation. Therefore, we...
While FGFR1 amplification has been described in breast cancer, the optimal treatment approach for FGFR1-amplified (FGFR1+) metastatic cancer (MBC) remains undefined.Experimental Design: We evaluated clinical response to endocrine and targeted therapies a cohort of patients with hormone receptor-positive (HR+)/HER2- MBC validated functional role FGFR1-amplification mediating response/resistance therapy vitro.In (N = 110), we identified that FGFR1+ tumors were more likely have progesterone...
Abstract Purpose: FGFR1 overexpression has been associated with endocrine resistance in ER+ breast cancer. We found localized the nucleus of cancer cells primary tumors resistant to estrogen suppression. investigated a role nuclear on gene transcription and antiestrogen resistance. Experimental Design: Tumors from patients treated letrozole were subjected Ki67 IHC. MCF7 transduced FGFR1(SP-)(NLS) promote overexpression. genomic activity ER+/FGFR1-amplified ± FOXA1 siRNA or FGFR tyrosine...
The MYC oncogene is frequently amplified in triple-negative breast cancer (TNBC). Here, we show that suppression induces immune-related hallmark gene set expression and tumor-infiltrating T cells MYC-hyperactivated TNBCs. Mechanistically, repressed stimulator of interferon genes (STING) via direct binding to the STING1 enhancer region, resulting downregulation T-cell chemokines CCL5, CXCL10, CXCL11. In primary metastatic TNBC cohorts, tumors with high or activity exhibited low STING...
Multiple lines of evidence support that the Hedgehog (Hh) signalling has a role in maintenance and progression different human cancers. Therefore, inhibition Hh pathway represents valid anticancer therapeutic approach for renal cell carcinoma (RCC) patients. NVP-LDE225 is Smoothened (Smo) antagonist induces dose-related Smo-dependent tumour growth. We assayed effects alone or combination with everolimus sunitinib on growth invasion RCC models both vitro vivo. To this aim, we used panel...
We developed neratinib-resistant HER2-mutant cancer cells by gradual dose escalation. RNA sequencing identified TORC1 signaling as an actionable mechanism of drug resistance. Primary and acquired neratinib resistance in breast patient-derived xenografts (PDXs) was also associated with hyperactivity. Genetic suppression RAPTOR or RHEB ablated P-S6 restored sensitivity to the tyrosine kinase inhibitor. The combination inhibitor everolimus potently arrested growth organoids established from...
Abstract The 17q23 amplicon is associated with poor outcome in ER + breast cancers, but the causal genes to endocrine resistance this are unclear. Here, we interrogate transcriptome data from primary tumors and find that among 17q23, PRR11 a key gene response therapeutic estrogen suppression. promotes estrogen-independent proliferation confers cancers. Mechanistically, proline-rich motif-mediated interaction of p85α regulatory subunit PI3K suppresses p85 homodimerization, thus enhancing...
Abstract Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) have been approved in combination with endocrine therapy (ET) to treat estrogen receptor-positive (ER+) metastatic breast cancer (BC). However, drug resistance represents the leading cause of patients mortality. This study aimed identify novel mechanisms ER antagonists CDK4/6 inhibitors. We generated two ER+ BC cell lines, T47D MCF7, resistant antagonist fulvestrant CDK4/6i abemaciclib, named T47D-FAR MCF7-FAR. Transcriptomic...
Small cell lung cancer (SCLC) is a highly aggressive form of with limited treatment options. Patients often respond well to initial chemo-immunotherapy but relapse quickly, necessitating new strategies enhance immune responsiveness. Recent research explores combining DNA-damaging therapies immunotherapy activate the STING pathway and improve antitumor response. The addition DNA Damage Repair (DDR) inhibitors, such as DNA-PKcs after chemotherapy has shown promise in activating innate sensors...