Ferdinandos Skoulidis
A5048517627- Lung Cancer Treatments and Mutations
- Colorectal Cancer Treatments and Studies
- Cancer Immunotherapy and Biomarkers
- RNA modifications and cancer
- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
- Chronic Lymphocytic Leukemia Research
- Lung Cancer Research Studies
- Advanced Breast Cancer Therapies
- Cancer-related Molecular Pathways
- Mycobacterium research and diagnosis
- Peptidase Inhibition and Analysis
- Lung Cancer Diagnosis and Treatment
- Cancer therapeutics and mechanisms
- Pancreatic and Hepatic Oncology Research
- Cancer Mechanisms and Therapy
- Chromatin Remodeling and Cancer
- Computational Drug Discovery Methods
- Calcium signaling and nucleotide metabolism
- Melanoma and MAPK Pathways
- PARP inhibition in cancer therapy
- DNA Repair Mechanisms
- Cell Adhesion Molecules Research
- HER2/EGFR in Cancer Research
- Cancer, Hypoxia, and Metabolism
The University of Texas MD Anderson Cancer Center
2016-2025
Texas Medical Center
2023
The University of Texas System
2021
National Institutes of Health
2019
The University of Texas Health Science Center at Houston
2019
Hutchison/MRC Research Centre
2008-2012
Medical Research Council
2011-2012
Addenbrooke's Hospital
2004-2012
University of Cambridge
2008-2012
Thoracic Surgery Foundation
2012
Abstract KRAS is the most common oncogenic driver in lung adenocarcinoma (LUAC). We previously reported that STK11/LKB1 (KL) or TP53 (KP) comutations define distinct subgroups of KRAS-mutant LUAC. Here, we examine efficacy PD-1 inhibitors these subgroups. Objective response rates to blockade differed significantly among KL (7.4%), KP (35.7%), and K-only (28.6%) (P < 0.001) Stand Up To Cancer (SU2C) cohort (174 patients) with LUAC patients treated nivolumab CheckMate-057 phase III...
Sotorasib showed anticancer activity in patients with KRAS p.G12C–mutated advanced solid tumors a phase 1 study, and particularly promising was observed subgroup of non–small-cell lung cancer (NSCLC).
Our previously published findings reported that local consolidative therapy (LCT) with radiotherapy or surgery improved progression-free survival (PFS) and delayed new disease in patients oligometastatic non-small-cell lung cancer (NSCLC) did not progress after front-line systemic therapy. Herein, we present the longer-term overall (OS) results accompanied by additional secondary end points.
The molecular underpinnings that drive the heterogeneity of KRAS-mutant lung adenocarcinoma are poorly characterized. We performed an integrative analysis genomic, transcriptomic, and proteomic data from early-stage chemorefractory identified three robust subsets dominated, respectively, by co-occurring genetic events in STK11/LKB1 (the KL subgroup), TP53 (KP), CDKN2A/B inactivation coupled with low expression NKX2-1 (TTF1) transcription factor (KC). further revealed biologically...
Abstract STK11/LKB1 is among the most commonly inactivated tumor suppressors in non–small cell lung cancer (NSCLC), especially tumors harboring KRAS mutations. Many oncogenes promote immune escape, undermining effectiveness of immunotherapies, but it unclear whether inactivation suppressor genes, such as STK11/LKB1, exerts similar effects. In this study, we investigated consequences loss on microenvironment a mouse model KRAS-driven NSCLC. Genetic ablation resulted accumulation neutrophils...
We previously demonstrated the association between epithelial-to-mesenchymal transition (EMT) and drug response in lung cancer using an EMT signature derived cell lines. Given contribution of tumor microenvironments to EMT, we extended our investigation patient tumors from 11 types develop a pan-cancer signature.Using signature, conducted integrated, global analysis genomic proteomic profiles associated with across 1,934 including breast, lung, colon, ovarian, bladder cancers. Differences...
Abstract Although treatment with immune checkpoint inhibitors provides promising benefit for patients cancer, optimal use is encumbered by high resistance rates and requires a thorough understanding of mechanisms. We observed that tumors treated PD-1/PD-L1 blocking antibodies develop through the upregulation CD38, which induced all-trans retinoic acid IFNβ in tumor microenvironment. In vitro vivo studies demonstrate CD38 inhibits CD8+ T-cell function via adenosine receptor signaling or...
Epidermal growth factor receptor (EGFR) mutations typically occur in exons 18-21 and are established driver non-small cell lung cancer (NSCLC)1-3. Targeted therapies approved for patients with 'classical' a small number of other mutations4-6. However, effective have not been identified additional EGFR mutations. Furthermore, the frequency effects atypical on drug sensitivity unknown1,3,7-10. Here we characterize mutational landscape 16,715 EGFR-mutant NSCLC, establish structure-function...
Abstract In KRAS-mutant lung adenocarcinoma, tumors with LKB1 loss (KL) are highly enriched for concurrent KEAP1 mutations, which activate the KEAP1/NRF2 pathway (KLK). Here, we investigated biological consequences of these cooccurring alterations and explored whether they conferred specific therapeutic vulnerabilities. Compared KL tumors, KLK exhibited increased expression genes involved in glutamine metabolism, tricarboxylic acid cycle, redox homeostasis signature. Using isogenic pairs...
In this phase I/II trial, we evaluated the safety and effectiveness of pembrolizumab, with or without concurrent radiotherapy (RT), for lung liver lesions from metastatic non-small cell cancer (mNSCLC).Patients amenable to RT plus at least one additional non-contiguous lesion were included regardless programmed death-ligand 1 (PD-L1) status. Pembrolizumab was given 200 mg every 3 weeks up 32 cycles RT. Metastatic treated stereotactic body (SBRT; 50 Gy in 4 fractions) if clinically feasible...
Background Non-small cell lung cancer (NSCLC) patients bearing targetable oncogene alterations typically derive limited benefit from immune checkpoint blockade (ICB), which has been attributed to low tumor mutation burden (TMB) and/or PD-L1 levels. We investigated oncogene-specific differences in these markers and clinical outcome. Methods Three cohorts of NSCLC with (n=4189 total) were analyzed. Two advanced treated ICB monotherapy [MD Anderson (MDACC; n=172) Flatiron Health-Foundation...
IntroductionProgrammed death-ligand 1 (PD-L1) expression may vary in different disease sites and at time points of the course. We aimed to investigate PD-L1 heterogeneity its usefulness as a predictive value for immune checkpoint inhibitor (ICI) therapy patients with NSCLC.MethodsPD-L1 was analyzed 1398 NSCLC. The ICIs 398 metastatic NSCLC assessed.ResultsPD-L1 significantly associated biopsy (p = 0.004). Adrenal, liver, lymph node (LN) metastases had highest continuous variable 1% or 50%...
Abstract Neoadjuvant ipilimumab + nivolumab (Ipi+Nivo) and chemotherapy (Nivo+CT) induce greater pathologic response rates than CT alone in patients with operable non-small cell lung cancer (NSCLC). The impact of adding to neoadjuvant Nivo+CT is unknown. Here we report the results correlates two arms phase 2 platform NEOSTAR trial testing Ipi+Nivo+CT major (MPR) as primary endpoint. MPR were 32.1% (7/22, 80% confidence interval (CI) 18.7–43.1%) arm 50% (11/22, CI 34.6–61.1%) arm; endpoint...
Molecular modifiers of KRASG12C inhibitor (KRASG12Ci) efficacy in advanced KRASG12C-mutant NSCLC are poorly defined. In a large unbiased clinicogenomic analysis 424 patients with non-small cell lung cancer (NSCLC), we identified and validated coalterations KEAP1, SMARCA4, CDKN2A as major independent determinants inferior clinical outcomes KRASG12Ci monotherapy. Collectively, comutations these three tumor suppressor genes segregated into distinct prognostic subgroups captured ∼50% those early...
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary point, may be published when key planned co-primary or secondary analyses are not yet available. Trial Updates provide an opportunity to disseminate additional results from studies, in JCO elsewhere, for which point has already been reported.In longest follow-up, our knowledge, a KRASG12C inhibitor, we assessed long-term efficacy, safety, and biomarkers of...