A5057005895- Cancer Genomics and Diagnostics
- Cancer Immunotherapy and Biomarkers
- Health Systems, Economic Evaluations, Quality of Life
- Colorectal Cancer Treatments and Studies
- Lung Cancer Treatments and Mutations
- Pancreatic and Hepatic Oncology Research
- Esophageal Cancer Research and Treatment
- Genetic factors in colorectal cancer
- Advanced Breast Cancer Therapies
- PARP inhibition in cancer therapy
- BRCA gene mutations in cancer
- Genomics and Rare Diseases
- Immune cells in cancer
- Pharmaceutical studies and practices
- Immune Cell Function and Interaction
- Pharmacovigilance and Adverse Drug Reactions
- Cancer Treatment and Pharmacology
- Statistical Methods in Clinical Trials
- Metastasis and carcinoma case studies
- Pharmaceutical Economics and Policy
- Chemokine receptors and signaling
- DNA Repair Mechanisms
- Cancer Cells and Metastasis
- COVID-19 and healthcare impacts
- Melanoma and MAPK Pathways
Oncode Institute
2019-2025
The Netherlands Cancer Institute
2017-2025
Dutch Cancer Society
2024
There is a clear and unmet clinical need for biomarkers to predict responsiveness chemotherapy cancer. We developed an in vitro test based on patient-derived tumor organoids (PDOs) from metastatic lesions identify nonresponders standard-of-care colorectal cancer (CRC). In prospective study, we show the feasibility of generating testing PDOs evaluation sensitivity chemotherapy. Our PDO predicted response biopsied lesion more than 80% patients treated with irinotecan-based therapies without...
Abstract Genomics has greatly improved how patients with cancer are being treated; however, clinical-grade genomic biomarkers for chemotherapies currently lacking. Using whole-genome analysis of 37 metastatic colorectal (mCRC) treated the chemotherapy trifluridine/tipiracil (FTD/TPI), we identified KRAS codon G12 ( ) mutations as a potential biomarker resistance. Next, collected real-world data 960 mCRC receiving FTD/TPI and validated that were significantly associated poor survival, also in...
Many patients with cancer exhibit primary or rapid secondary resistance to targeted therapy (TT). We hypothesized that a higher number of altered oncogenic signaling pathways [pathway alteration load (PAL)] would reduce the benefit TT which only intervenes in one pathway. This hypothesis was tested Drug Rediscovery Protocol (DRUP). DRUP is prospective, pan-cancer, non-randomized clinical trial (NCT02925234) treats therapy-refractory metastatic and an actionable molecular profile using...
Abstract Purpose: Patients with rare cancers (incidence less than 6 cases per 100,000 persons year) commonly have treatment opportunities and are understudied at the level of genomic targets. We hypothesized that patients cancer benefit from approved anticancer drugs outside their label similar to common cancers. Experimental Design: In Drug Rediscovery Protocol (DRUP), therapy-refractory metastatic harboring an actionable molecular profile matched FDA/European Medicines Agency–approved...
Abstract The Dutch Drug Rediscovery Protocol (DRUP) and the Australian Cancer Molecular Screening Therapeutic (MoST) Program are similar nonrandomized, multidrug, pan‐cancer trial platforms that aim to identify signals of clinical activity molecularly matched targeted therapies or immunotherapies outside their approved indications. Here, we report results for advanced metastatic cancer patients with tumors harboring cyclin D‐CDK4/6 pathway alterations treated CDK4/6 inhibitors palbociclib...
Abstract Background ‘Precision oncology’ can ensure the best suitable treatment at right time by tailoring towards individual patient and comprehensive tumour characteristics. In current molecular pathology, diagnostic tests which are part of standard care (SOC) only cover a limited spectrum genomic changes, often performed in an iterative way. This occurs expense valuable time, available tissue sample, interferes with ‘first right’ decisions. Whole Genome Sequencing (WGS) captures near...
Interrogating the stochastic events underlying tumor evolution from non-malignant precursors is crucial for understanding therapy resistance. Current methods are complicated by chromosomal instability, obscuring driver identification and yielding non-representative genetics. Inspired patient tumors that evolve without we developed Stochastically Emergent Tumors (SETs) inducing mismatch repair deficiency in precursors, then engrafting mice. Barcoded SETs exhibited increased tumoral drug...
Abstract Recent studies have identified a link between specific microbiome-derived bacteria and immune checkpoint blockade (ICB) efficacy. However, these species lack consistency across their immunomodulatory mechanisms remain elusive. We hypothesized that community-level metabolic pathways microbes are more suitable to predict ICB response. Using curated resource of pan-cancer metagenomics data ICB-treated patients, we several microbial processes significantly associated with...
Abstract Background In this study we aimed to evaluate the efficacy and safety of PD-L1 inhibitor durvalumab across various mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) tumours in Drug Rediscovery Protocol (DRUP). This is a clinical which patients are treated with drugs outside their labeled indication, based on tumour molecular profile. Patients methods dMMR/MSI-H solid who had exhausted all standard care options were eligible. durvalumab. The primary...
Abstract In the Drug Rediscovery Protocol (DRUP), patients with cancer are treated based on their tumor molecular profile approved targeted and immunotherapies outside labeled indication. Importantly, undergo a biopsy for whole‐genome sequencing (WGS) which allows WGS‐based evaluation of routine diagnostics. Notably, we observed that not all biopsies dMMR/MSI‐positive tumors as determined by diagnostics were classified microsatellite‐unstable subsequent WGS. Therefore, aimed to evaluate...
Although eligibility criteria are essential in trial design, overly restrictive contribute to low accrual and limited generalizability. To enhance inclusivity, there has been growing interest broadening criteria, especially for patients with advanced or treatment-refractory disease. Yet, the impact on patient safety remains uncertain. In Drug Rediscovery Protocol (DRUP), protocol exceptions frequently requested occasionally granted. Here we describe of these waivers treatment efficacy.
2590 Background: Microsatellite unstable (MSI) tumors represent 4% of all cancer diagnoses and are known to be sensitive immune checkpoint inhibitors (ICI). Despite the progress made, a significant proportion patients with MSI does not respond, highlighting urgent need identify additional predictive biomarkers. In this study, we evaluated efficacy PD-1 inhibitor nivolumab across pre-treated solid performed extensive biomarker analysis better characterize ICI-effectiveness in setting....
To evaluate the efficacy of pembrolizumab across multiple cancer types harboring different levels whole-genome sequencing-based tumor mutational load (TML; total nonsynonymous mutations genome) in patients included Drug Rediscovery Protocol (NCT02925234).