Search results for "1506"
showing 10 items of 235 documents
In the literature: June 2018
2018
Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) are a highly active family of compounds that have changed the scenario in ovarian and human epidermal growth factor receptor 2 (HER2) non-amplified breast cancer management in the recent years. Despite impressive clinical activity, a prolonged treatment with PARPi is frequently associated with acquired resistance to this therapy. The identification of mechanisms and strategies to overcome resistance are crucial. Bromodomain containing 4 (BRD4) is a member of the bromodomain and extraterminal (BET) protein family that facilitates oncogenic transcription. BRD4 is frequently amplified in high-grade serous ovarian cancer (HGSOC) and can be …
In the literature: June 2020.
2020
Immunotherapy based on checkpoint blockade has revolutionised cancer treatment during last years. Whereas this approach fails in a relevant group of patients, the knowledge on tumour microenvironment (TME) opened the possibility to the use of additional therapeutic strategies to potentiate antitumour immunity, including depletion of protumourigenic or immune suppressive and activation of specific immune populations using agonistic antibodies. Nevertheless, due to the complexity of the TME, many of these strategies have been indiscriminately advanced to the clinic without clear mechanistic hypotheses. Nowadays, single-cell RNA sequencing (scRNA-seq)-based transcriptome analyses identify T ce…
Aurora kinases in ovarian cancer
2020
Aurora kinases (AURK) are key regulators of the mitotic spindle formation. AURK is frequently overexpressed in ovarian cancer and this overexpression has been frequently associated with prognosis in these tumours. Interestingly, AURK have been shown to interact with DNA repair mechanisms and other cell cycle regulators. These functions have brought light to Aurora family as a potential target for anticancer therapy. In the last years, two clinical trials with different AURK inhibitors have shown activity in epithelial and clear-cell ovarian cancer. Although there is a lack of predictive factors of AURK inhibition activity, recent trials have identified some candidates. This review will focu…
In the literature: December 2019
2020
The introduction of new high-throughput technologies in oncology and the need to apply precision medicine for cancer patients has led to the detection of several molecular alterations. Among them, activating mutations of ERBB2 have been reported in many solid tumours. In the last years, several clinical trials with covalent tyrosine kinase inhibitors (TKIs) for ERBB2 mutant cancers have been conducted, with different results among several cancer types. In the SUMMIT trial, neratinib was most effective in breast cancer patients, with the majority of responders having tumours with L755S, V777L, or L869R ERBB2 mutations.1 In an elegant article published in C ancer C ell by Robichaux et al ,2 d…
In the literature: February 2020.
2020
The phosphatidylinositol-3-kinase (PI3K)/Akt and the mammalian target of rapamycin (mTOR) signaling pathways is one of the most frequently deregulated pathways in human cancers. This pathway controls multiple cellular processes, including metabolism, motility, proliferation, growth and survival. It can be aberrantly activated through multiple mechanisms, including diverse genomic alterations involving oncogenes and tumour suppressor genes.1 These alterations offer opportunities for therapeutic targeting of the pathway. PI3Kα protein complex is composed of regulatory (p85α) and catalytic (p110α) subunits. Pik3ca codes for p110α, which is the most frequently mutated oncogene across different …
Management of orphan symptoms: ESMO Clinical Practice Guidelines for diagnosis and treatment†
2020
### Highlights There is no clear definition of orphan symptoms. There is a group of symptoms that are seldom evaluated in most symptom assessment tools which can be considered as orphan symptoms.1 These are generally prevalent symptoms that are unaddressed in clinical practice, yet often not reported by the patients or by healthcare professionals.2 Orphan symptoms may be defined as symptoms not regularly assessed in clinical practice, and consequently little studied and not properly treated. No epidemiological or clinical studies generally exist to gauge the prevalence of the symptoms chosen; nevertheless, these symptoms are distressing for patients and their families. Orphan symptoms remai…
In the literature: August 2020.
2020
Immune checkpoint inhibitors (ICI) have become a key component of therapy for several solid tumours. In patients diagnosed with advanced clear cell renal cell carcinoma (ccRCC), immunotherapy has always been considered as a treatment option, and anti-PD-1-based therapies are approved in both the frontline and refractory settings. Response to PD-1 blockade has been associated with numerous tumour-intrinsic and microenvironment features. Genetic characterisation of ccRCC has significantly contributed to the knowledge of tumour biology and the mechanisms of disease progression, but the interplay of genomic alterations with patterns of immune infiltration in response to PD-1 blockade remains un…
Overall survival at 5 years of follow-up in a phase III trial comparing ipilimumab 10 mg/kg with 3 mg/kg in patients with advanced melanoma
2020
BackgroundWe have previously reported significantly longer overall survival (OS) with ipilimumab 10 mg/kg versus ipilimumab 3 mg/kg in patients with advanced melanoma, with higher incidences of adverse events (AEs) at 10 mg/kg. This follow-up analysis reports a 5-year update of OS and safety.MethodsThis randomized, multicenter, double-blind, phase III trial included patients with untreated or previously treated unresectable stage III or IV melanoma. Patients were randomly assigned (1:1) to ipilimumab 10 mg/kg or 3 mg/kg every 3 weeks for 4 doses. The primary end point was OS.ResultsAt a minimum follow-up of 61 months, median OS was 15.7 months (95% CI 11.6 to 17.8) at 10 mg/kg and 11.5 mont…
In the literature: April 2017
2017
The full publication in Lancet Oncology of the Stockholm III trial helps us to understand that short-course radiotherapy in patients with localised rectal cancer could also be followed by delayed surgery.1 During more than 14 years, more than 800 patients with rectal cancer not showing unresectable features were randomised in a two-arm versus three-arm study with a non-inferiority design. Patients could be randomised to short-course radiotherapy (5×5 Gy) and immediate (within a week) versus delayed (4–8 weeks) surgery. In the three-arm randomisation patients could also be allocated to a long course of concurrent chemoradiation (25×2 Gy), with surgery performed 6–8 weeks thereafter. Time to …
In the literature: May 2016
2016
Radiotherapy as single modality was considered the standard of care for low-grade gliomas, a mixed population of low proliferative tumours including oligodendrogliomas, oligoastrocytomas and grade 2 astrocytomas. However, a recently reported trial in the New England Journal of Medicine indicates1 that the addition of procarbacine, lomustine (CCNU) and vincristine, a combination known by its acronym, PCV, significantly prolongs survival in patients with low-grade glioma. When this trial was initially reported in 2012, after a median follow-up of almost 6 years, according to the estimated number of events needed to analyse the results, a significant difference in progression-free survival (PF…