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395
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Introduction
Current institution
Additional affiliations
July 2008 - October 2014
March 2005 - July 2008
January 2004 - February 2005
University of California, San Francisco, UCSF
Position
- Senior Researcher
Description
- Wnt signaling pathways in NSCLC
Publications
Publications (395)
e23141
Background: Neoadjuvant and perioperative chemoimmunotherapy is increasingly used in resectable NSCLC. Several trials achieved improvement in EFS and OS and most used a perioperative strategy . There is poor compliance of post-op IT and its duration, cost and value are not well established. Here we report a pharmacoeconomic analysis of NADIM...
8084
Background: Pleural mesothelioma (PM) is an aggressive malignancy that harbors significant inter- and intra-tumoral heterogeneity. Spatial transcriptomics enables the dissection of the tumor's molecular architecture by facilitating compartment-specific gene expression profiling. We performed high-resolution RNA-seq analysis of tumor (Tm) and s...
Background
Non-small cell lung cancer (NSCLC) is the most common lung cancer subtype and the leading cause of cancer-related deaths worldwide. Advances in treatment have focused on personalized approaches that use targeted therapies and immunotherapies based on protein, DNA, or RNA biomarkers. Assessing molecular biomarkers typically takes 1-2 week...
Background
Lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) are the most common lung cancer subtypes. SCC is traditionally resistant to anti-angiogenic therapies, though the mechanisms remain unclear. Nintedanib, a multi-angiokinase receptor inhibitor, is approved for treating ADC in combination with docetaxel, based on selective efficac...
Perioperative chemoimmunotherapy (ChIO) has become a paradigm shift in the treatment of patients with locally advanced non-small cell lung cancer (NSCLC), considerably increasing complete pathological response (CPR) and survival rates. The role played by B lymphocytes in the antitumor response emerges as a crucial factor in the fight against cancer...
Background
Tarlatamab, a bispecific T-cell engager immunotherapy targeting delta-like ligand 3, has demonstrated promising survival outcomes in small-cell lung cancer (SCLC). Given the risk of cytokine release syndrome (CRS), initial clinical trials incorporated 48-72-h inpatient monitoring in cycle 1.
Methods
Patients with previously treated SCLC...
ALK (anaplastic lymphoma kinase) rearrangements represent the third most predominant driver oncogene in non-small cell lung cancer (NSCLC). Although ALK inhibitors are the tyrosine kinase inhibitors (TKIs) with the longest survival rates in lung cancer, the complex systemic clinical evaluation and the apoptotic cell death evasion of drug-tolerant p...
Immune checkpoint blockers (ICBs) have revolutionized the treatment of non–small cell lung cancer (NSCLC). Currently, one-dose-fits-all maximalist regimens have been considered the standard of care, with ICBs administered at flat doses regardless of patients’ weight. Treatment duration with ICBs is often arbitrary across stages, ranging from a fixe...
Purpose
To determine the effectiveness of uni- or multimodal prehabilitation on several outcomes in patients undergoing neoadjuvant therapy before cancer surgery.
Methods
A systematic search was carried on May 1, 2023, using four major databases (SCOPUS, Web of Science, Medline (Ovid and Pubmed)) and updated monthly until February 2024. Inclusion...
Introduction: Complex structural remodelling of cells and extracellular matrix during cancer initiation and progression elicit substantial biomechanical alterations, which can be measured by Atomic Force Microscopy (AFM) at the nanoscale level. Clinical and translational evidence indicates that tissue nanomechanical signature (NS) can be a useful t...
Introduction: The balance and composition of the gut microbiome play a pivotal role in modulating the host immune system, and they have been associated with survival outcomes in patients undergoing immunotherapy-based treatments and immune-related adverse events. In this study, our objective was to analyze the fecal microbiota of non-small-cell lun...
The fibrotic tumor microenvironment is a pivotal therapeutic target. Nintedanib, a clinically approved multikinase antifibrotic inhibitor, is effective against lung adenocarcinoma (ADC) but not squamous cell carcinoma (SCC). Previous studies have implicated the secretome of tumor‐associated fibroblasts (TAFs) in the selective effects of nintedanib...
The treatment landscape of resectable early-stage non-small cell lung cancer (NSCLC) is set to change significantly due to encouraging results from randomized trials evaluating neoadjuvant and adjuvant immunotherapy, as well as adjuvant targeted therapy. As of January 2024, marketing authorization has been granted for four new indications in Europe...
The treatment landscape of resectable early-stage non-small cell lung cancer (NSCLC) is transforming due to the approval of novel adjuvant and neoadjuvant systemic treatments. The European Medicines Agency (EMA) recently approved adjuvant osimertinib, adjuvant atezolizumab, adjuvant pembrolizumab, and neoadjuvant nivolumab combined with chemotherap...
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO...
Introduction
RET inhibitors with impressive overall response rates are now available for patients with NSCLC, yet the identification of RET fusions remains a difficult challenge. Most guidelines encourage the upfront use of next-generation sequencing (NGS), or alternatively, fluorescence in situ hybridization (FISH) or reverse transcriptase-polymer...
Introduction:
Chemotherapy-induced nausea and vomiting (CINV) is one of the adverse events that most affects oncologic patients' quality of life. Carboplatin AUC ≥ 4 belongs to agents with high emetic risk (moderate risk in ASCO guidelines). We aimed to compare the effectiveness of netupitant/palonosetron and dexamethasone triple combination (TC)...
Introduction:
There are currently three first-line immunotherapy options used as monotherapy in advanced non-small cell lung cancer (NSCLC) patients with high programmed death ligand 1 (PD-L1) expression (≥50%). This manuscript aims to evaluate the available data on atezolizumab (AT), cemiplimab (CEMI), and pembrolizumab (PEMBRO) and to study the...
Background
Drugs targeting the spindle assembly checkpoint (SAC), such as inhibitors of Aurora kinase B (AURKB) and dual specific protein kinase TTK, are in different stages of clinical development. However, cell response to SAC abrogation is poorly understood and there are no markers for patient selection.
Methods
A panel of 53 tumor cell lines o...
Small-cell lung cancer (SCLC) is a highly aggressive malignancy comprising approximately 15% of lung cancers. Only one-third of patients are diagnosed at limited-stage (LS). Surgical resection can be curative in early stages, followed by platinum-etoposide adjuvant therapy, although only a minority of patients with SCLC qualify for surgery. Concurr...
Background:
Approximately 20% of patients with non-small-cell lung cancer (NSCLC) receive a diagnosis of stage III disease. There is no current consensus regarding the most appropriate treatment for these patients.
Methods:
In this open-label, phase 2 trial, we randomly assigned patients with resectable stage IIIA or IIIB NSCLC to receive neoadj...
ALK, ROS1 and RET fusions and MET∆ex14 variant associate with response to targeted therapies in non-small cell lung cancer (NSCLC). Technologies for fusion testing in tissue must be adapted to liquid biopsies, which are often the only material available. In this study, circulating-free RNA (cfRNA) and extracellular vesicle RNA (EV-RNA) were purifie...
Adenocarcinoma (ADC) and Squamous Cell Carcinoma (SCC) are the most frequent histologic subtypes of lung cancer, and both are rich in activated/myofibroblast-like tumor-associated fibroblasts (TAFs). Nintedanib is a potent antifibrotic drug that targets the tumor stroma and is clinically approved to treat advanced lung ADC patients owing to the sur...
Background: Lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) are the most common histologic subtypes in lung cancer. Intriguingly, ADC and SCC exhibit distinct responses to the multi-tyrosine kinase inhibitor nintedanib and other antiangiogenic drugs, suggesting that angiogenesis may depend on the histologic subtype in lung cancer. In ad...
Lung cancer is characterized by a stiff fibrotic microenvironment rich in activated/pro-fibrotic tumor-associated fibroblasts (TAFs). We previously reported a larger accumulation of TAFs in lung adenocarcinoma (ADC) compared to lung squamous cell carcinoma (SCC), the two most frequent lung cancer subtypes. However, the underlying mechanisms remain...
Background:
The APPLE trial aimed to evaluate the feasibility of longitudinal plasma EGFR T790M monitoring for the best sequencing strategy of gefitinib and osimertinib.
Methods:
APPLE is a randomized, non-comparative, phase II study in patients with common EGFR-mutant, treatment-naïve NSCLC including 3-arms: Arm A (osimertinib upfront until REC...
Background:
In patients with non-small cell lung cancer (NSCLC), the presence of abnormal hiliar lymph nodes (clinical N1; cN1), central tumor location and/or tumor size (diameter >3 cm) increases the risk of occult mediastinal metastasis (OMM). This study investigates prospectively the diagnostic value of an integral mediastinal staging (IMS) str...
Purpose
Small cell lung cancer (SCLC) is an aggressive malignancy with limited treatments. Delta-like ligand 3 (DLL3) is aberrantly expressed in most SCLC. Tarlatamab (AMG 757), a bispecific T cell engager molecule, binds both DLL3 and CD3 leading to T cell-mediated tumor lysis. Herein, we report phase 1 results of tarlatamab in patients with SCLC....
Background
The TGF-β1 transcription factor SMAD3 is epigenetically repressed in tumour-associated fibroblasts (TAFs) from lung squamous cell carcinoma (SCC) but not adenocarcinoma (ADC) patients, which elicits a compensatory increase in SMAD2 that renders SCC-TAFs less fibrotic. Here we examined the effects of altered SMAD2/3 in fibroblast migratio...
Limited strategies are available at disease progression on osimertinib for patients with EGFR-mutant non-small-cell lung cancer. The emergence of the on-target EGFR C797S mutation has been described as one of the most common mechanisms of resistance. Additionally, loss of the EGFR T790M mutation has also been mainly investigated as a resistance phe...
Purpose/Objective(s)
Primary analysis (database cutoff, Oct 28, 2020) of the global KEYNOTE-799 study (NCT03631784) in patients (pts) with unresectable, locally advanced stage III NSCLC, showed that pembrolizumab (pembro; anti–PD-1) + cCRT resulted in an ORR of 70.5% in cohort A (n = 112; squamous and nonsquamous) and 70.6% in cohort B (n = 102; no...
Objectives
To determine the incidence of ALK translocations in patients with advanced/metastatic NSCLC in Spain, to describe the clinical characteristics of these patients, and to evaluate the effectiveness and safety of treatment with crizotinib in a real-world setting.
Methods
This is an observational prospective and retrospective cohort study t...
Tissue inhibitor of metalloproteinase-1 (TIMP-1) is an important regulator of extracellular matrix turnover that has been traditionally regarded as a potential tumor suppressor owing to its inhibitory effects of matrix metalloproteinases. Intriguingly, this interpretation has been challenged by the consistent observation that increased expression o...
10569
Background: Preliminary data has highlighted inherited predisposition to lung cancer (LC) related to certain pathogenic germline variant (PGV) in cancer predisposing genes, including patients (pts) with tumors harboring somatic driver oncogene alterations (alt); however, the frequency of PGV in LC is unknown. Liquid biopsy assays may be able...
8508
Background: Primary analysis (database cutoff, Oct 28, 2020) of the global KEYNOTE-799 study (NCT03631784) in patients (pts) with unresectable, locally advanced stage III NSCLC, showed that pembrolizumab (pembro; anti–PD-1) plus cCRT resulted in an ORR of 70.5% in cohort A (n = 112; squamous and nonsquamous) and 70.6% in cohort B (n = 102; non...
8501
Background: Non-small cell lung cancer (NSCLC) is incurable in most patients with locally advanced stage IIIA disease. Previous results indicate that the use of neoadjuvant chemoimmunotherapy could increase the percentage of cured patients being a promising therapeutic option that has to be tested in randomized clinical trials. Methods: NADIM...
Objectives: Exercise has been reported to alleviate disease as well as treatment impact in patients with lung cancer. Nevertheless, there is limited information available regarding the perception of lung cancer dedicated healthcare professionals’ and their advice on exercise.
Materials and Methods: An online survey exploring healthcare professiona...
Background
: Concurrent chemoradiotherapy is a standard therapy for patients with stage III non-small cell lung cancer (NSCLC). Durvalumab is an approved treatment option following concurrent chemoradiotherapy in the absence of disease progression. The global, phase 3, randomized, placebo- and active-controlled, double-blind KEYLYNK-012 study evalu...
Introduction
Combination of anti-EGFR monoclonal antibodies or immune checkpoint inhibitors with TKIs has shown minimal benefit in EGFR mutant (EGFR-mut) NSCLC patients. Consequently, new combination approaches are needed.
Patients and Methods
The EPICAL was a single arm, phase 1b study to evaluate safety, tolerability and anti-tumor activity of f...
Background: The role of perfusion computed tomography (pCT) in detecting changes in tumor vascularization as part of a response to antiangiogenic therapy in non-small cell lung cancer (NSCLC) remains unclear. Methods: In this prospective pilot study (IMPACT trial, NCT02316327), we aimed to determine the ability of pCT to detect early changes in blo...
Purpose/Objective(s)
KEYNOTE-799 (NCT03631784), a phase 2 study of the anti‒PD-1 antibody pembrolizumab (pembro) plus concurrent chemoradiation therapy (cCRT) in patients (pts) with unresectable, locally advanced stage III NSCLC, completed accrual and follow up is ongoing. Results in a subset of pts from this study showed an ORR of 69.6% in cohort...
Purpose/Objective(s)
Pembrolizumab, an anti‒PD-1 antibody is standard of care therapy for metastatic non‒small-cell lung cancer (NSCLC) as monotherapy and in combination with chemotherapy. Durvalumab, an anti–PD-L1 antibody, is approved for unresectable, stage III NSCLC without disease progression following CCRT. Early trials of pembrolizumab in co...
PurposeThe aim of our study was to investigate the correlation between cfDNA concentration and fragment size fraction with FDG PET/CT- and CT-derived parameters in untreated NSCLC patient.Methods
Fifty-three patients diagnosed of locally advanced or metastatic NSCLC who had undergone FDG PET/CT, CT and cfDNA analysis prior to any treatment were inc...
Lung cancer is the leading cause of cancer-related death worldwide. The desmoplastic stroma of lung cancer and other solid tumors is rich in tumor-associated fibroblasts (TAFs) exhibiting an activated/myofibroblast-like phenotype. There is growing awareness that TAFs support key steps of tumor progression and are epigenetically reprogrammed compare...
The cobas® EGFR Test provides a semiquantitative index (SQI) that reflects the proportion of mutated versus wild-type copies of the EGFR gene in plasma. The significance of SQI as an indirect measure of the variant allele frequency (VAF) or mutated copies/mL remains unclear. The aim of this study was to evaluate the correlation of SQI with the VAF...
The two most common lung cancer subtypes are adenocarcinoma (ADC) and squamous cell carcinoma (SCC). Even though both subtypes are epithelial in origin, it is now clear that tumor associated fibroblasts (TAFs) are key regulators of tumor progression and response to therapies. Nintedanib is an antifibrotic drug that targets the tumor stroma and has...
Background: Fusion involving anaplastic lymphoma kinase (ALK), RET proto-oncogene (RET) or ROSproto-oncogene 1, receptor tyrosine kinase (ROS1), neurotrophic receptor tyrosine kinase 1 (NTRK1)and neuregulin 1 (NRG1) are present in lung cancer (LC) and represent important biomarkers fortargeted therapies. However, little is known about the RNA expre...
Large cell carcinoma (LCC) is an aggressive lung cancer subtype with poor prognosis and no targeted therapies. We previously reported that tumor-associated fibroblasts (TAFs) derived from LCC tumors exhibit premature senescence, and coculture of pulmonary fibroblasts with LCC cell lines selectively induces fibroblast senescence, which in turn drive...
Background: We have recently demonstrated that antibodies generated by vaccination (anti-EGFVacAbs) potentiate the effects of EGFR TKIs in epidermal growth factor receptor mutant (EGFR-mut) non-small cell lung cancer (NSCLC) cells growing in vitro and prevent the emergence of resistance to EGFRTKIs (1). Based on these preclinical results we have st...
Despite impressive and durable responses, non‐small cell lung cancer (NSCLC) patients treated with anaplastic lymphoma kinase inhibitors (ALK‐Is) ultimately progress due to development of resistance. Here, we have evaluated the clinical utility of circulating tumor DNA (ctDNA) profiling by next‐generation sequencing (NGS) upon disease progression....
Importance
Administration of pembrolizumab plus concurrent chemoradiation therapy (cCRT) may provide treatment benefit to patients with locally advanced, stage III non–small cell lung cancer (NSCLC).
Objective
To evaluate treatment outcomes and safety of pembrolizumab plus cCRT in stage III NSCLC.
Design, Setting, and Participants
The phase 2, no...
Background:
To systematically assess the consistency of recommendations regarding diagnosis and treatment of non-small cell lung cancer (NSCLC) in clinical practice guidelines (CPGs).
Methods:
We systematically searched relevant literature databases and websites to identify CPGs related to NSCLC. We extracted the general characteristics of the i...
8512
Background: KEYNOTE-799 (NCT03631784) is an ongoing study of the anti‒PD-1 antibody pembrolizumab (pembro) plus concurrent chemoradiation therapy (cCRT) in patients (pts) with unresectable, locally advanced stage III NSCLC. Prior results from this study in a subset of pts (primary efficacy population) showed an ORR of 69.6% in cohort A (squamo...
TPS8580
Background: Pembrolizumab, an anti‒PD-1 antibody is standard of care therapy for metastatic non‒small-cell lung cancer (NSCLC) as monotherapy and in combination with chemotherapy. Durvalumab, an anti–PD-L1 antibody, is approved for unresectable, stage III NSCLC without disease progression following concurrent chemoradiation therapy (CCRT)....
Clinical guidelines promote the identification of several targetable biomarkers to drive treatment decisions in advanced non-small cell lung cancer (NSCLC), but half of all patients do not have a viable biopsy. Specimens from endobronchial-ultrasound transbronchial needle aspiration (EBUS-TBNA) are an alternative source of material for the initial...
Large cell carcinoma (LCC) is a rare and aggressive lung cancer subtype with poor prognosis and no targeted therapies. Tumor-associated fibroblasts (TAFs) derived from LCC tumors exhibit premature senescence, and coculture of pulmonary fibroblasts with LCC cell lines selectively induces fibroblast senescence, which in turn drives LCC cell growth an...
Background
Pleural effusion (PE) is a common metastatic site of NSCLC, associated with poor outcomes. As very few data are available about immune checkpoint inhibitors (ICI) and PE, we aimed to assess the clinical outcome of PE in NSCLC treated with ICI.
Method
Multicenter international retrospective study of patients with metastatic NSCLC treated...
