A5038414970- Lung Cancer Research Studies
- Membrane-based Ion Separation Techniques
- Cancer therapeutics and mechanisms
- Metal-Organic Frameworks: Synthesis and Applications
- Neuroendocrine Tumor Research Advances
- Cancer Genomics and Diagnostics
- Membrane Separation Technologies
- Cancer Cells and Metastasis
- Colorectal Cancer Treatments and Studies
- Catalytic Processes in Materials Science
- Lung Cancer Treatments and Mutations
- MicroRNA in disease regulation
- Peptidase Inhibition and Analysis
- Radio Frequency Integrated Circuit Design
- Chemical Analysis and Environmental Impact
- Melanoma and MAPK Pathways
- Nanomaterials for catalytic reactions
- DNA and Nucleic Acid Chemistry
- Drug Transport and Resistance Mechanisms
- Polyomavirus and related diseases
- Toxin Mechanisms and Immunotoxins
- Cancer Research and Treatments
- Mathematical Biology Tumor Growth
- Mechanisms of cancer metastasis
- Neuroblastoma Research and Treatments
Cancer Research UK Manchester Institute
2016-2024
University of Manchester
2016-2024
CRUK Lung Cancer Centre of Excellence
2024
Cancer Research UK
2024
Candiolo Cancer Institute
2013-2015
Istituti di Ricovero e Cura a Carattere Scientifico
2015
University of Turin
2013-2014
Colorectal cancers that become resistant to EGFR inhibitors through a variety of mechanisms can be effectively treated by inhibiting MEK in conjunction with EGFR.
Abstract Purpose: Introduced in 1987, platinum-based chemotherapy remains standard of care for small cell lung cancer (SCLC), a most aggressive, recalcitrant tumor. Prominent barriers to progress are paucity tumor tissue identify drug targets and patient-relevant models interrogate novel therapies. Following our development circulating patient–derived explants (CDX) as that faithfully mirror patient disease, here we exploit CDX examine new therapeutic options SCLC. Experimental Design: We...
Abstract Molecular targeted drugs are clinically effective anti-cancer therapies. However, tumours treated with single agents usually develop resistance. Here we use colorectal cancer (CRC) as a model to study how the acquisition of resistance EGFR-targeted therapies can be restrained. Pathway-oriented genetic screens reveal that CRC cells escape from EGFR blockade by downstream activation RAS-MEK signalling. Following treatment anti-EGFR, anti-MEK or combination two drugs, find alone...
Small cell lung cancer (SCLC) is an aggressive disease with median survival of <2 years. Tumour biopsies for research are scarce, especially from extensive-stage patients, repeat sampling at progression rarely performed. We overcame this limitation relevant preclinical models by developing SCLC circulating tumour derived explants (CDX), which mimic the donor pathology and chemotherapy response. To facilitate compound screening identification clinically biomarkers, we developed short-term ex...
ABSTRACT Molecular subtypes of Small Cell Lung Cancer (SCLC) have been described based on differential expression transcription factors (TFs) ASCL1, NEUROD1 , POU2F3 and immune-related genes. We previously reported an additional subtype the neurogenic TF ATOH1 within our SCLC Circulating tumour cell- Derived eXplant (CDX) model biobank. Here we show that protein was detected in 7/81 preclinical models 16/102 clinical samples SCLC. In CDX models, directly regulated neurogenesis...
Most small cell lung cancer (SCLC) patients are initially responsive to cytotoxic chemotherapy, but almost all undergo fatal relapse with progressive disease, highlighting an urgent need for improved therapies and better patient outcomes in this disease. The proapoptotic BH3 mimetic ABT-737 that targets BCL-2 family proteins demonstrated good single-agent efficacy preclinical SCLC models. However, so far clinical trials of the Navitoclax have been disappointing. We previously inhibition a...
Abstract Small cell lung cancer (SCLC) has a 5-year survival rate of <7%. Rapid emergence acquired resistance to standard platinum-etoposide chemotherapy is common and improved therapies are required for this recalcitrant tumour. We exploit six paired pre-treatment post-chemotherapy circulating tumour patient-derived explant (CDX) models from donors with extensive stage SCLC investigate changes at disease progression after chemotherapy. Soluble guanylate cyclase (sGC) recurrently...
Abstract Monoclonal antibodies targeting EGFR are used in the clinic to treat KRAS wild type metastatic colorectal cancer (CRC). After an initial response, secondary resistance occurs thereby limiting clinical benefit of these drugs. Relapsed patients have no further therapeutic options, therefore, elucidating molecular basis is a prerequisite for development lines therapy. We took advantage from panel CRC cell sensitive inhibition by treating with cetuximab or panitumumab until resistant...
Abstract Serial biopsies of solid tumors can be challenging, not always without risk to the patient and do capture intratumoral heterogeneity. ‘Liquid Biopsies’ in form Circulating Tumor DNA (ctDNA) Cells (CTCs) offer minimally invasive means stratify patients for therapy routinely monitor responses anticipate emergent resistance. Whilst technically more challenging than ctDNA, CTCs a wider range biomarker application allowing RNA protein measurements within single pools following enrichment...
Abstract Occurence of acquired resistance constitutes one the major limitations to tumor treatment. In colorectal cancer, use anti-EGFR antibodies such as cetuximab and panitumumab is effective in only 15-20% patients, till secondary targeted treatment develops. Shedding light on molecular basis represents then a mandatory effort order foster new lines therapy. We recently showed that KRAS mutations are responsible for emergence EGFR therapy subset CRC patients (Misale et al., Nature 2012)....
<p>Supplementary Figure 1. Combination treatment with olaparib/AZD1775 is effective in select SCLC CDX models. Mice bearing CDX3 (a), CDX4 (b), CDX8 (c), or CDX8p (d) tumors were treated vehicles (black) AZD1775 (red), olaparib (green), the combination (blue) for 21 days. Each line depicts an individual relative tumor volume from all mice. e) topotecan (blue). Topotecan was administered on days 1-3 and 1-21. Supplementary 2. more chemoresistant than CDX8. a) The clinical timeline...
<p>Supplementary Figure 1. Combination treatment with olaparib/AZD1775 is effective in select SCLC CDX models. Mice bearing CDX3 (a), CDX4 (b), CDX8 (c), or CDX8p (d) tumors were treated vehicles (black) AZD1775 (red), olaparib (green), the combination (blue) for 21 days. Each line depicts an individual relative tumor volume from all mice. e) topotecan (blue). Topotecan was administered on days 1-3 and 1-21. Supplementary 2. more chemoresistant than CDX8. a) The clinical timeline...
<div>Abstract<p><b>Purpose:</b> Introduced in 1987, platinum-based chemotherapy remains standard of care for small cell lung cancer (SCLC), a most aggressive, recalcitrant tumor. Prominent barriers to progress are paucity tumor tissue identify drug targets and patient-relevant models interrogate novel therapies. Following our development circulating patient–derived explants (CDX) as that faithfully mirror patient disease, here we exploit CDX examine new therapeutic...
<div>Abstract<p><b>Purpose:</b> Introduced in 1987, platinum-based chemotherapy remains standard of care for small cell lung cancer (SCLC), a most aggressive, recalcitrant tumor. Prominent barriers to progress are paucity tumor tissue identify drug targets and patient-relevant models interrogate novel therapies. Following our development circulating patient–derived explants (CDX) as that faithfully mirror patient disease, here we exploit CDX examine new therapeutic...
<p>Supplementary Figure 3. H524 cytotoxicity</p>
<p>Supplementary Figure 5. Bcl2 family expression</p>
<div>Abstract<p>Most small cell lung cancer (SCLC) patients are initially responsive to cytotoxic chemotherapy, but almost all undergo fatal relapse with progressive disease, highlighting an urgent need for improved therapies and better patient outcomes in this disease. The proapoptotic BH3 mimetic ABT-737 that targets BCL-2 family proteins demonstrated good single-agent efficacy preclinical SCLC models. However, so far clinical trials of the Navitoclax have been disappointing....
<p>Supplementary Figure 7. In vivo tolerance study</p>
<p>Supplementary Figure 8. PI3K signaling in CDX2</p>
<p>Supplementary Figure 1. BMX expression in SCLC</p>
<p>Supplementary Figure 5. Bcl2 family expression</p>