Clinical Trial Protocol for VIOLET: A Single-Center, Phase I/II Trial Evaluation of Radioligand Treatment in Patients with Metastatic Castration-Resistant Prostate Cancer with [Tb]Tb-PSMA-I&T.

[Lu]Lu-PSMA is an effective class of therapy for patients with metastatic castration-resistant prostate cancer (mCRPC); however, progression is inevitable. The limited durability of response may be partially explained by the presence of micrometastatic deposits, which are energy-sheltered and receive low absorbed radiation with Lu due to the approximately 0.7-mm mean pathlength.

YBX1 integration of oncogenic PI3K/mTOR signalling regulates the fitness of malignant epithelial cells.

In heterogeneous head and neck cancer (HNC), subtype-specific treatment regimens are currently missing. An integrated analysis of patient HNC subtypes using single-cell sequencing and proteome profiles reveals an epithelial-mesenchymal transition (EMT) signature within the epithelial cancer-cell population. The EMT signature coincides with PI3K/mTOR inactivation in the mesenchymal subtype.

Arginine-rich C9ORF72 ALS proteins stall ribosomes in a manner distinct from a canonical ribosome-associated quality control substrate.

Hexanucleotide expansion mutations in C9ORF72 are a frequent cause of amyotrophic lateral sclerosis. We previously reported that long arginine-rich dipeptide repeats (DPRs), mimicking abnormal proteins expressed from the hexanucleotide expansion, caused translation stalling when expressed in cell culture models. Whether this stalling provides a mechanism of pathogenicity remains to be determined.

AlphaBet: Combination of Radium-223 and [ Lu]Lu-PSMA-I&T in men with metastatic castration-resistant prostate cancer (clinical trial protocol).

Background: [Lu]Lu-PSMA is a radioligand therapy used in metastatic castration-resistant prostate cancer (mCRPC). Despite a survival benefit, the responses for many patients receiving [Lu]Lu-PSMA are not durable, and all patients eventually develop progressive disease. The bone marrow is the most common site of progression.

Regulation of gene expression via translational buffering.

Translation of an mRNA represents a critical step during the expression of protein-coding genes. As mechanisms governing post-transcriptional regulation of gene expression are progressively unveiled, it is becoming apparent that transcriptional programs are not fully reflected in the proteome. Herein, we highlight a previously underappreciated post-transcriptional mode of regulation of gene expression termed translational buffering.