Search results for "Tumour heterogeneity"
showing 8 items of 8 documents
Towards precision oncology for HER2 blockade in gastroesophageal adenocarcinoma
2019
Gastroesophageal adenocarcinoma (GEA) represents a very heterogeneous disease and patients in advanced stages have a very poor prognosis. Although several molecular classifications have been proposed, precision medicine for HER2-amplified GEA patients still represents a challenge. Despite improvement in clinical outcomes obtained by adding trastuzumab to first-line platinum-based chemotherapy, no other anti-HER2 agents used first-line or beyond progression have demonstrated any benefit. Several factors contribute to this failure. Among them, variable HER2 amplification assessment, tumour heterogeneity, molecular mechanisms of resistance and microenvironmental factors could limit the effecti…
Epigenomic landscape of human colorectal cancer unveils an aberrant core of pan-cancer enhancers orchestrated by YAP/TAZ
2021
Cancer is characterized by pervasive epigenetic alterations with enhancer dysfunction orchestrating the aberrant cancer transcriptional programs and transcriptional dependencies. Here, we epigenetically characterize human colorectal cancer (CRC) using de novo chromatin state discovery on a library of different patient-derived organoids. By exploring this resource, we unveil a tumor-specific deregulated enhancerome that is cancer cell-intrinsic and independent of interpatient heterogeneity. We show that the transcriptional coactivators YAP/TAZ act as key regulators of the conserved CRC gained enhancers. The same YAP/TAZ-bound enhancers display active chromatin profiles across diverse human t…
Intra-tumour heterogeneity of diffuse large B-cell lymphoma involves the induction of diversified stroma-tumour interfaces
2020
Abstract Background Intra-tumour heterogeneity in lymphoid malignancies encompasses selection of genetic events and epigenetic regulation of transcriptional programs. Clonal-related neoplastic cell populations are unsteadily subjected to immune editing and metabolic adaptations within different tissue microenvironments. How tissue-specific mesenchymal cells impact on the diversification of aggressive lymphoma clones is still unknown. Methods Combining in situ quantitative immunophenotypical analyses and RNA sequencing we investigated the intra-tumour heterogeneity and the specific mesenchymal modifications that are associated with A20 diffuse large B-cell lymphoma (DLBCL) cells seeding of d…
Analytical Validation of Multiplex Biomarker Assay to Stratify Colorectal Cancer into Molecular Subtypes
2019
International audience; Previously, we classified colorectal cancers (CRCs) into five CRCAssigner (CRCA) subtypes with different prognoses and potential treatment responses, later consolidated into four consensus molecular subtypes (CMS). Here we demonstrate the analytical development and validation of a custom NanoString nCounter platform-based biomarker assay (NanoCRCA) to stratify CRCs into subtypes. To reduce costs, we switched from the standard nCounter protocol to a custom modified protocol. The assay included a reduced 38-gene panel that was selected using an in-house machine-learning pipeline. We applied NanoCRCA to 413 samples from 355 CRC patients. From the fresh frozen samples (n…
PO-324 Detection of high-risk prostate cancer biomarkers by RNA sequencing and qPCR method
2018
Introduction New prognostic biomarkers for prostate cancer have the potential to overcome the clinical challenge of therapy decision and overtreatment. Present diagnostic and prognostic tests are still limited in specificity resulting in a large number of false positives and unnecessary biopsies. Furthermore, they do not enable a proper stratification between men with a high risk for an aggressive disease course requiring comprehensive therapy scheme after surgery and men with a low risk of disease recurrence cured after prostatectomy or eligible for active surveillance. In particular, patients with Gleason score 6 and 7 tumours (low and mid stage) are difficult to stratify for the appropri…
In the literature: April 2018
2018
The most important aim of precision medicine is the selection of the best treatment for each individual patient. To achieve this objective, the analysis of the molecular changes that can occur due to tumour heterogeneity or after anticancer treatment is fundamental. A dynamical study of the disease could lead to the identification of specific targets, which need to be inhibited at time of tumour progression. By using high-throughput sequencing, it is possible to identify a very limited number of somatic mutations that can be exploited for cancer treatment and drug development. However, the ability to predict response to targeted agents needs to be further improved. To do this, parallel stud…
Prognostic markers in low-grade papillary urothelial neoplasms of the urinary bladder: an update
2009
Abstract Papillary urothelial neoplasms of the urinary bladder comprise a heterogeneous spectrum of ‘continuous' lesions in which the assessment of an accurate histological grade and tumour stage is mandatory for the clinical management of patients. The 1998 World Health Organization/International Society of Urologic Pathologists (WHO/ISUP) consensus classification and the 1999 WHO classification proposed new malignancy grading schemes, mainly based on morphometric studies for the replacement of the 1973 WHO grading system. In accordance with these novel grading systems, two major categories of papillary urothelial neoplasms were distinguished: low-grade and high-grade papillary urothelial …
18F-FDG PET for breast cancer : combined analysis of tumour perfusion and metabolism for tumour characterisation and neoadjuvant chemotherapy respons…
2020
Neoadjuvant chemotherapy (NAC) is a common treatment in patients with locally advanced or large breast cancer at diagnosis. A pathological complete response (pCR) at the end of NAC is recognized as a good surrogate marker of relapse-free survival. An early identification of the pathological response has then become a key parameter to monitor new therapeutic strategies. Studies, focusing on predictive biomarkers identification, have shown that early changes in tumour metabolism, assessed by Positron Emission Tomography (PET) using 2-desoxy-2-18F-fluoro-D-glucose (18F-FDG), allow the early assessment of the pathological response at the end of treatment. However, given the diversity of breast …