Search results for "1506"
showing 10 items of 235 documents
Assessing molecular subtypes of gastric cancer: microsatellite unstable and Epstein-Barr virus subtypes. Methods for detection and clinical and patho…
2018
Background The molecular classification of gastric cancer recognises two subtypes prone to immune checkpoint blockade: the microsatellite unstable and the Epstein-Barr virus (EBV)-related tumours. We aim to assess the concordance between immunohistochemistry and PCR for microsatellite status evaluation, and explore the value of microsatellite instability (MSI) and EBV as predictive survival factors. Material and methods We collected 246 consecutively diagnosed gastric cancer cases in all stages and evaluated the microsatellite status using immunohistochemistry for mismatched repair (MMR) proteins and PCR. EBV expression was studied through in situ hybridisation. Results Forty-five (18%) cas…
In the literature: February 2018
2018
Non-invasive liquid biopsies may transform the management of patients with cancer. Circulating tumour DNA (ctDNA) derived from cancer cells can be identified in most patients with advanced cancer, representing a potential non-invasive source of tumour DNA. The analysis of ctDNA may be useful to genotype the cancer, to select treatment options and to monitor response to treatment. ctDNA is often at a low level in plasma, requiring highly sensitive and accurate assays for ctDNA analysis. ctDNA was detected and profiled together with primary tumour DNA obtained from surgical specimens in 40 patients with lung cancer with localised disease who were diagnosed at stages I–III and operated on with…
In the literature: October 2019
2019
Gastrointestinal cancers are a subset of molecularly heterogeneous diseases. In the era of personalised medicine, major efforts are being made towards stratifying patients according to molecular profiling. However, although most treatments are currently based on targeted therapy in relation to specific genomic alterations, acquired resistance emerges during anticancer therapies and subsequently treatment failure occurs. Intratumour heterogeneity plays a significant role in the acquisition of resistance by clonal evolution of tumour cell populations under therapeutic pressure. Despite a single tumour biopsy represents the standard for cancer research and drives our therapeutic decisions, lim…
In the literature: April 2019
2019
Glioblastoma (GBM) remains an unmet need in Medical Oncology considering its poor prognosis and the lack of advances in therapeutics in more than one decade.1 Despite the initial enthusiasm, the development of immunotherapy in GBM has proved to be challenging, with a disappointing negative phase III clinical trial.2 Some of the phenotypic hallmarks of GBM make immunotherapy difficult. Its relatively low mutational load, its immunologically ‘cold’ microenvironment with scarce infiltrating immune effector cells, a dominant myeloid compartment composed by microglia and myeloid-derived suppressor cells and a strong immunosuppression, both local, mediated by immunosuppressive regulatory T cells …
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…
In the literature: October 2020.
2020
Immune checkpoint inhibitors are widely used as treatment for an increasing number of solid tumours. Nevertheless, the lack of predictive biomarker represents a limitation across several cancer types. During the last years, the possibility to dynamically study tumour evolution through circulating tumour DNA (ctDNA) in plasma has opened novel possibility in evaluating disease status and therapeutic response, especially in localised disease to predict the possibility of relapse. However, the specific opportunities for application in the context of immunotherapy remain to be clarified.1 In an article recently published in Cancer Discovery by Zhang et al ,2 a comprehensive analysis of ctDNA dat…
In the literature: October 2018
2018
Several trials with the check-point inhibitors pembrolizumab or nivolumab demonstrated some antitumour efficacy in chemorefractory advanced gastric cancer with a response rate ranging from 10% to 26%. However, no clear predictive biomarkers were found to facilitate a proper selection of patients. A series of 61 patients with advanced gastric cancer received second-line or third-line treatment with pembrolizumab in a prospective phase 2 trial.1 In a cooperative effort carried out by Korean and American investigators, a molecular characterisation of all tumours was performed including whole-exome sequencing and RNA sequencing of tissue biopsies, as well as circulating tumour DNA (ctDNA) from …
Shortening adjuvant chemotherapy in stage III colon cancer: are we ready for a change?
2018
Oxaliplatin-based adjuvant chemotherapy for 6 months is considered the standard of care after a curative resection in patients with stage III colon cancer. The addition of oxaliplatin provides a benefit on overall survival confirmed in three randomised phase 3 trials1–3 with an long-term absolute increase ranging from 2.7% to 6%. Since oxaliplatin was incorporated into the adjuvant setting more than a decade ago, the standard in adjuvant therapy has remained unchanged because of the lack of novel agents with relevant activity in this scenario. Unfortunately, this combination can have also acute and long-term side effects that can interfere with daily life activities in potentially cured pat…
In the literature: December 2018
2018
The current development of immune checkpoint modulatory treatments has shown durable responses in the treatment of multiple cancer types.1 However, predictive biomarkers beyond PD-1 ligand 1 (PD-L1) expression and high microsatellite instability (MSI-H) to stratify patients and identify those who could benefit of these therapies are needed. In this sense, a recent study published in Science by Cristescu et al 2 describes the potential usefulness of combining the tumour mutational burden (TMB) and the T cell-inflamed gene expression profile (GEP) to jointly predict clinical response to pembrolizumab. Both PD-L1 and the GEP represent a T cell-inflamed tumour microenvironment (TME), whereas TM…
In the literature: June 2019
2019
Biliary tract cancer (BTC) includes cholangiocarcinoma and gallbladder cancer. BTCs are known to have a poor prognosis, with a 5-year overall survival below 20%.1 Unfortunately, majority of patients are diagnosed with advanced stage, being palliative chemotherapy with cisplatin and gemcitabine the current standard of care.2 Poor prognosis is due to the fact that only 20% of patients are diagnosed in early stages3 and the high risk of relapse following curative surgery. Unfortunately, the lack of randomised studies has made the role of adjuvant treatment in BTC following surgery an unresolved matter for many years.4 5 Adjuvant therapy (either in the form of chemotherapy or chemoradiotherapy)…