The current approval indications for pembrolizumab are complex, reflecting the inclusion criteria of numerous clinical trials that led to approvals. Here we argue that allowing the use of pembrolizumab to any advanced solid tumor in any tumor type in any line of therapy for a fixed duration may be preferable to the current assortment of indications...
Alpha-fetoprotein (AFP) is expressed by stem-like and poor outcome hepatocellular cancer tumors and is a clinical tumor biomarker. AFP has been demonstrated to inhibit dendritic cell differentiation and maturation and to block oxidative phosphorylation. To identify the critical metabolic pathways leading to human dendritic cell functional suppressi...
The KRAS oncogene is present in up to 25% of solid tumors and for decades had been undruggable. Sotorasib was the first-in-class KRAS inhibitor to reach the US and European market, and its pharmacological inhibition is restricted to the KRAS p.G12C mutation. Sotorasib showed activity (tumor shrinkage) in patients with non-small cell lung cancer har...
Concerns have been raised that regulatory programs to accelerate approval of cancer drugs in cancer may increase uncertainty about benefits and harms for survival and quality of life (QoL). We analyzed all pivotal clinical trials and all non-pivotal randomized controlled trials (RCTs) for all cancer drugs approved for the first time by the FDA betw...
Diffuse Midline Glioma (DMG) which includes Diffuse Intrinsic Pontine Glioma (DIPG) is an infiltrative tumor of the midline structures of the central nervous system that demonstrates an aggressive pattern of growth and has no known curative treatment. As these tumors progress, children experience ongoing neurological decline including inability to ...
IntroductionWe sought to characterise oncology basket and umbrella trials that have been implemented, determine how many have been completed, and calculate the response rate, by tumour type and drug target.MethodsWe conducted a retrospective, cross-sectional review of PubMed, Embase, and clinicaltrials.gov for all oncology basket and umbrella trial...
Previous estimates of the likelihood of a drug tested in phase I trials obtaining FDA clearance are out of date. In the intervening years, newer pharmaceuticals have been developed, resulting in new delivery systems and lines of therapies. We sought to explore and update these estimates by comprehensively searching drugs tested in phase I trials an...
Even though a cadre of agents that inhibit transforming growth factor β (TGFβ) is being tested in cancer patients, clinical benefit from TGFβ inhibition has not yet been achieved. The myriad mechanisms in which TGFβ is protumorigenic may be a key obstacle to its effective deployment; cancer cells frequently employ TGFβ-regulated programs that engen...
BackgroundThe utilization of basket trials in oncology has gained popularity because of the drive for precision medicine and the increasing ease of genetically profiling tumors. However, it is unknown if this has translated into patient benefit, either through higher response rates because of precision treatment or because of increasing options for...
The generation of vascular stroma is essential for solid tumor growth and involves stimulatory and inhibiting factors as well as stromal components that regulate functions such as cellular adhesion, migration, and gene expression. In an effort to obtain a more integrated understanding of vascular stroma formation in breast carcinoma, we examined ex...
