A5018105485- HER2/EGFR in Cancer Research
- Lung Cancer Treatments and Mutations
- Monoclonal and Polyclonal Antibodies Research
- PI3K/AKT/mTOR signaling in cancer
- Cancer, Hypoxia, and Metabolism
- Growth Hormone and Insulin-like Growth Factors
- Cancer-related Molecular Pathways
- Melanoma and MAPK Pathways
- Metabolism, Diabetes, and Cancer
- Protease and Inhibitor Mechanisms
- Chronic Lymphocytic Leukemia Research
- Advanced Breast Cancer Therapies
- RNA modifications and cancer
- Liver physiology and pathology
- Colorectal Cancer Treatments and Studies
- Hepatocellular Carcinoma Treatment and Prognosis
- Cell Adhesion Molecules Research
- Cancer Cells and Metastasis
- Cancer Treatment and Pharmacology
- Glycosylation and Glycoproteins Research
- Skin Protection and Aging
- Fibroblast Growth Factor Research
- Caveolin-1 and cellular processes
- Cancer Research and Treatments
- Blood groups and transfusion
Isdin (Spain)
2024-2025
Universitat Autònoma de Barcelona
2010-2023
The University of Texas MD Anderson Cancer Center
2006-2023
Hebron University
2010-2023
Vall d'Hebron Institute of Oncology
2009-2016
Vall d'Hebron Hospital Universitari
2009-2016
Memorial Sloan Kettering Cancer Center
2010-2014
Vall d'Hebron Institut de Recerca
2011-2014
AVEO Oncology (United States)
2014
GlaxoSmithKline (Belgium)
2013
Uncontrolled proliferation is a hallmark of cancer. In breast cancer, immunohistochemical assessment the proportion cells staining for nuclear antigen Ki67 has become most widely used method comparing between tumor samples. Potential uses include prognosis, prediction relative responsiveness or resistance to chemotherapy endocrine therapy, estimation residual risk in patients on standard therapy and as dynamic biomarker treatment efficacy samples taken before, during, after neoadjuvant...
There is a strong rationale to therapeutically target the phosphatidylinositol 3-kinase/protein kinase B/mammalian of rapamycin (PI3K/AKT/mTOR) pathway in breast cancer since it highly deregulated this disease and also mediates resistance anti-HER2 therapies. However, initial studies with rapalogs, allosteric inhibitors mTORC1, have resulted limited clinical efficacy probably due release negative regulatory feedback loop that triggers AKT ERK signaling. Since activation occurs via PI3K, we...
Clinical benefits from trastuzumab and other anti-HER2 therapies in patients with HER2 amplified breast cancer remain limited by primary or acquired resistance. To identify potential mechanisms of resistance, we established trastuzumab-resistant cells chronic exposure to treatment. Genomewide copy-number variation analyses the resistant compared parental revealed a focal amplification genomic DNA containing cyclin E gene. In cohort 34 + treated trastuzumab-based therapy, found that...
We investigated whether mutations in the gene encoding phosphatidylinositol 3-kinase (PI3K) catalytic subunit (PIK3CA) correlates with response to neoadjuvant human epidermal growth factor receptor 2 (HER2) -targeted therapies patients breast cancer.Baseline tissue biopsies were available from HER2-positive early cancer who enrolled onto Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial (NeoALTTO). Activating PIK3CA identified using mass spectrometry-based...
FUS1 is a tumor suppressor gene located on human chromosome 3p21, and expression of Fus1 protein highly regulated at various levels, leading to lost or greatly diminished function in many lung cancers. Here we show that selected microRNAs (miRNA) interact with the 3'-untranslated region (3'UTR) FUS1, down-regulation expression. Using computational methods, first predicted target three miRNAs, miR-93, miR-98, miR-197, then showed exogenous overexpression these miRNAs inhibited We confirmed...
Abstract The development of new modes diagnosis and targeted therapy for lung cancer is dependent on the identification unique cell surface features cells isolation reagents that bind with high affinity specificity to these biomarkers. We recently isolated a 20-mer peptide which binds adenocarcinoma line, H2009, from phage-displayed library. show here cellular receptor this peptide, TP H2009.1, uniquely expressed integrin, αvβ6, binding lines correlates integrin expression. able mediate...
To determine the frequency of estrogen receptor alpha and beta progesterone protein immunohistochemical expression in a large set non-small cell lung carcinoma (NSCLC) specimens to compare our results with those for some same antibodies that have provided inconsistent previously published reports.Using multiple antibodies, we investigated receptors 317 NSCLCs placed tissue microarrays correlated their patients' clinicopathologic characteristics adenocarcinomas EGFR mutation status.Estrogen...
A subgroup of human epidermal growth factor receptor 2 (HER2)-overexpressing breast tumors coexpresses p95HER2, a truncated HER2 that retains highly functional kinase domain but lacks the extracellular and results in intrinsic trastuzumab resistance. We hypothesized lapatinib, tyrosine inhibitor, would be active these tumors. have studied correlation between p95HER2 expression response to both preclinical models clinical setting.Two different animal were used for studies. Expression was...
The PI3K signaling pathway regulates diverse cellular processes, including proliferation, survival, and metabolism, is aberrantly activated in human cancer. As such, numerous compounds targeting the are currently being clinically evaluated for treatment of cancer, several have shown some early indications efficacy breast However, resistance against these agents, both de novo acquired, may ultimately limit compounds. Here, we taken a systematic functional approach to uncovering potential...
Insulin-like growth factor-1 receptor (IGF-1R) mediates cellular processes in cancer and has been proposed as a therapeutic target. Dalotuzumab (MK-0646) is humanized IgG1 monoclonal antibody that binds to IGF-1R preventing activation. This study was designed evaluate the safety tolerability of dalotuzumab, determine pharmacokinetic (PK) pharmacodynamic (PD) profiles, identify recommended phase II dose.Patients with tumors expressing protein were allocated dose-escalating cohorts three or...
Abstract Purpose: Up-regulation of the receptor tyrosine kinase EphA2 has been shown in several epithelial cancers. Epidermal growth factor (EGFR) and K-Ras have reported to regulate vitro models, but this regulation never examined tumors from patients. Because established importance EGFR mutations non–small cell lung cancer (NSCLC), we investigated relationship between these type. The significance expression was further by testing for correlation with other clinical parameters. Experimental...
Abstract Purpose: Expression of p95HER2 has been associated with resistance to trastuzumab-based therapy in patients metastatic breast cancer. Conversely, high levels HER2 have linked increased clinical benefit from anti-HER2 therapy. In this work, we aimed investigate whether the and can predict response Experimental Design: We measured by VeraTag HERmark, respectively, primary tumors enrolled neoadjuvant phase III study NeoALTTO correlated these variables pathologic complete (pCR)...
Clinical experience increasingly suggests that molecular prescreening and biomarker enrichment strategies in phase I trials with targeted therapies will improve the outcomes of patients cancer. In keeping exigencies a personalized oncology program, tumors from advanced chemorefractory colorectal cancer were analyzed for specific aberrations (KRAS/BRAF/PIK3CA mutations, PTEN pMET expression). Patients subsequently offered matched agents (MTA) directed at identified anomalies. During 2010...
The oncogenic PI3K/Akt/mTOR pathway is an attractive therapeutic target in cancer. However, it unknown whether the blockade required for tumor growth inhibition clinically achievable. Therefore, we conducted pharmacodynamic studies with GDC-0068, ATP competitive, selective Akt1/2/3 inhibitor, preclinical models and patients treated this compound.We used a reverse phase protein array (RPPA) platform to identify biomarker set indicative of Akt cell lines human-tumor xenografts, correlated...
Abstract Purpose: FUS1, a novel tumor-suppressor gene located in the chromosome 3p21.3 region, may play an important role lung cancer development. Currently, FUS1-expressing nanoparticles have been developed for treating patients with cancer. However, expression of Fus1 protein has not examined large series cancers and their sequential preneoplastic lesions. Experimental Design: Using tissue microarrays, we immunohistochemical 281 non–small cell carcinoma (NSCLC) 22 small specimens...
Abstract Overexpression of the receptor tyrosine kinase EphA2 occurs in non–small cell lung cancer (NSCLC) and a number other human cancers. This overexpression correlates with poor prognosis, smoking, presence Kirsten rat sarcoma (K-Ras) mutations NSCLC. In cancers, has been implicated migration metastasis. To determine if can promote NSCLC progression, we examined relationship proliferation lines metastases patient tumors. We also potential mechanisms involving AKT, Src, focal adhesion...
3008 Background: RIDA is a non-prodrug rapamycin analog mTOR inhibitor, and DALO humanized monoclonal antibody targeting the IGF-1R receptor. In preclinical models, dual mTOR/IGF1-R inhibition results in synergistic antitumor activity inhibits feedback AKT activation due to TORC1 by analogs. Methods: Pts with advanced cancers who failed standard therapy received at escalating doses of 10-40 mg/day QD×5/week combined 10 mg/kg/week or 7.5 mg/kg every other week. was administered for one week...
Abstract Insulin-like growth factor (IGF)-I receptor (IGF-IR) signaling has been implicated in several human neoplasms. However, the role of serum levels IGFs lung cancer risk is controversial. We assessed tissue-derived carcinogenesis. found that IGF-I and IGF-II bronchial tissue specimens containing high-grade dysplasia were significantly higher than those normal epithelium, hyperplasia, squamous metaplasia. Derivatives epithelial cell lines with activation mutation KRAS(V12) or loss p53...