A5109602065- Lung Cancer Treatments and Mutations
- Cancer Genomics and Diagnostics
- Lung Cancer Research Studies
- Colorectal Cancer Treatments and Studies
- Lung Cancer Diagnosis and Treatment
- Cancer Immunotherapy and Biomarkers
- Radiomics and Machine Learning in Medical Imaging
- Head and Neck Cancer Studies
- Gastric Cancer Management and Outcomes
- HER2/EGFR in Cancer Research
- RNA modifications and cancer
- Advanced Breast Cancer Therapies
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Cancer Cells and Metastasis
- Pancreatic and Hepatic Oncology Research
- PI3K/AKT/mTOR signaling in cancer
- Cancer therapeutics and mechanisms
- Lymphoma Diagnosis and Treatment
- Hepatocellular Carcinoma Treatment and Prognosis
- Brain Metastases and Treatment
- Genetic factors in colorectal cancer
- Cytokine Signaling Pathways and Interactions
- Microfluidic and Bio-sensing Technologies
- Epigenetics and DNA Methylation
- Colorectal and Anal Carcinomas
National Cancer Centre Singapore
2015-2024
Agency for Science, Technology and Research
2017-2024
Duke-NUS Medical School
2021-2024
Genome Institute of Singapore
2015-2024
SingHealth Duke-NUS Academic Medical Centre
2023
National University of Singapore
2023
Forest and Wood Products (Australia)
2021
SingHealth
2021
University of California San Francisco Medical Center
2019
Tokyo National Hospital
2019
Presence and frequency of rare circulating tumor cells (CTCs) in bloodstreams cancer patients are pivotal to early detection treatment monitoring. Here, we use a spiral microchannel with inherent centrifugal forces for continuous, size-based separation CTCs from blood (Dean Flow Fractionation (DFF)) which facilitates easy coupling conventional downstream biological assays. Device performance was optimized using cell lines (> 85% recovery), followed by clinical validation positive enumeration...
RET fusions are oncogenic drivers in 1 to 2% of non-small-cell lung cancers (NSCLCs). In patients with fusion-positive NSCLC, the efficacy and safety selective inhibition unknown.We enrolled advanced NSCLC who had previously received platinum-based chemotherapy those were untreated separately a phase 1-2 trial selpercatinib. The primary end point was an objective response (a complete or partial response) as determined by independent review committee. Secondary points included duration...
The enumeration and characterization of circulating tumor cells (CTCs), found in the peripheral blood cancer patients, provide a potentially accessible source for diagnosis prognosis. This work reports on novel spiral microfluidic device with trapezoidal cross-section ultra-fast, label-free enrichment CTCs from clinically relevant volumes. technique utilizes inherent Dean vortex flows present curvilinear microchannels under continuous flow, along inertial lift forces which focus larger...
The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines diagnosis, treatment and follow-up metastatic non-small-cell lung cancer (NSCLC) was published in 2016. At ESMO Asia Meeting November 2017 it decided by both Chinese (CSCO) to convene a special guidelines meeting immediately after Thoracic Group Annual 2018, Guangzhou, China. aim adapt 2016 take into account ethnic differences associated with NSCLC Asian patients. These represent...
BACKGROUND The current study was performed to report the long‐term results of a trial comparing concurrent chemotherapy and radiotherapy (CCRT) with surgery adjuvant (RT) in patients stage III/IV nonmetastatic head neck squamous cell carcinoma. METHODS Patients resectable carcinoma were randomized followed by RT or CCRT. halted prematurely due poor accrual. Human papillomavirus status tested on archival material using polymerase chain reaction sequencing. RESULTS Of total 119 patients, 60...
Background Circulating tumor cells (CTCs) are cancer that can be isolated via liquid biopsy from blood and phenotypically genetically characterized to provide critical information for guiding treatment. Current analysis of CTCs is hindered by the throughput, selectivity specificity devices or assays used in CTC detection isolation. Methodology/Principal Findings Here, we enriched putative samples patients with both advanced stage metastatic breast lung cancers using a novel multiplexed...
Rearranged during transfection (RET) gene fusions are a validated target in non-small-cell lung cancer (NSCLC). RET-selective inhibitors selpercatinib (LOXO-292) and pralsetinib (BLU-667) recently demonstrated favorable antitumor activity safety profiles advanced RET fusion-positive NSCLC, both have received approval by the US Food Drug Administration for this indication. Insights into mechanisms of resistance to selective remain limited.This study was performed at five institutions. Tissue...
Lymphocyte-activation gene 3 (LAG-3) is an inhibitory immunoreceptor that negatively regulates T-cell activation. This paper presents preclinical characterization of the LAG-3 inhibitor, ieramilimab (LAG525), and phase I data for treatment patients with advanced/metastatic solid tumors ±the anti-programmed cell death-1 antibody, spartalizumab.
Abstract Purpose: We report the intracranial efficacy of selpercatinib, a highly potent and selective RET inhibitor, approved in United States for fusion-positive non–small cell lung cancers (NSCLC). Patients Methods: In global phase 1/2 LIBRETTO-001 trial (NCT03157128) advanced RET-altered solid tumors, selpercatinib was dosed orally (160 mg twice every day) 28-day cycles. with baseline metastases had MRI/CT scans 8 weeks 1 year (12 thereafter). this pre-planned analysis patients NSCLC...
We demonstrate the high-throughput and high-resolution separation of rare circulating tumor cells (CTCs) from blood using a multiplexed spiral microfluidic device.
Anaplastic lymphoma kinase (ALK) rearrangements are important therapeutic targets in non-small cell lung cancer (NSCLC) that confer sensitivity to the ALK inhibitors crizotinib and ceritinib. To determine outcome of sequential treatment with crizotinb ceritinib, we retrospectively evaluated a cohort ALK-positive patients treated both agents.
Abstract EGFR -mutant lung adenocarcinomas (LUAD) display diverse clinical trajectories and are characterized by rapid but short-lived responses to tyrosine kinase inhibitors (TKIs). Through sequencing of 79 spatially distinct regions from 16 early stage tumors, we show that despite low mutation burdens, Asian LUADs unexpectedly exhibit a complex genomic landscape with frequent whole-genome doubling, aneuploidy, high clonal diversity. Multiple truncal alterations, including TP53 mutations...
9004 Background: Capmatinib is a highly potent and selective MET inhibitor. Previous data of GEOMETRY mono-1 study showed clinically meaningful overall response rate (ORR) manageable toxicity profile in patients (pts) with METΔex14–mutated NSCLC who received 1–2 prior lines treatment (tx) (Cohort 4) particular high ORR tx-naïve pts 5b). Here we report the results for duration (DOR) progression-free survival (PFS) as well updated ORR. Methods: phase 2, multi-cohort, multicenter evaluating...
Mesenchymal epithelial transition factor ( MET) activation has been implicated as an oncogenic driver in epidermal growth receptor EGFR)-mutant non-small-cell lung cancer (NSCLC) and can mediate primary secondary resistance to EGFR tyrosine kinase inhibitors (TKI). High copy number thresholds have suggested enrich for response MET inhibitors. We examined the clinical relevance of gain (CNG) setting treatment-naive metastatic EGFR-mutant-positive NSCLC.
9008 Background: RET fusions are targetable oncogenic drivers in up to 2% of NSCLC, yet no selective inhibitors approved. BLU-667 is an investigational highly potent and inhibitor targeting alterations, including those that confer resistance multikinase (MKIs). We provide update on the registration-enabling ARROW study (NCT03037385) pts with RET-fusion+ NSCLC. Methods: The global includes DE (30-600 mg daily [QD or BID]) dose expansion (DX) at recommended phase 2 (RP2D; 400 QD) advanced...
Abstract Background This multicenter, open-label, phase Ib study investigated the safety and efficacy of binimetinib (MEK inhibitor) in combination with buparlisib (phosphatidylinositol 3-kinase [PI3K] patients advanced solid tumors RAS/RAF alterations. Materials Methods Eighty-nine were enrolled study. Eligible had disease progression after standard therapy and/or for which no existed. Evaluable was mandatory, per RECIST version 1.1 Eastern Cooperative Oncology Group performance status 0-2....
9515 Background: Pralsetinib is an investigational, highly potent, selective RET kinase inhibitor targeting oncogenic alterations. We provide the registrational dataset for pts with fusion+ NSCLC and without prior treatment from global ARROW study. Methods: (75 sites in 11 countries; NCT03037385) consists of a phase I dose escalation to establish recommended II (400 mg once daily [QD] orally) expansion cohorts defined by tumor type and/or alteration. Primary objectives were overall response...
Abstract Purpose: Nasopharyngeal carcinoma is endemic in Asia and angiogenesis important for growth progression. We hypothesized that pazopanib would have antiangiogenic activity nasopharyngeal carcinoma. Experimental Design: A single arm monotherapy study of patients with WHO type II/III who had metastatic/recurrent disease failed at least one line chemotherapy. Simon's optimal 2-stage design was used. Patients Eastern Cooperative Oncology Group (ECOG) 0-2 adequate organ function were...
Genomics-driven cancer therapeutics has gained prominence in personalized treatment. However, its utility indications lacking biomarker-driven treatment strategies remains limited. Here we present a "phenotype-driven precision-oncology" approach, based on the notion that biological response to perturbations, chemical or genetic, ex vivo patient-individualized models can serve as predictive biomarkers for therapeutic clinic. We generated library of "screenable" patient-derived primary...