Impact of co-mutations and transcriptional signatures in non-small cell lung cancer patients treated with adagrasib in the KRYSTAL-1 trial.

Background: KRAS inhibitors are revolutionizing the treatment of NSCLC, but clinico-genomic determinants of treatment efficacy warrant continued exploration.

Methods: Patients with advanced KRASG12C-mutant NSCLC treated with adagrasib (KRYSTAL-1-NCT03785249) were included in the analysis. Pre-treatment NGS data were collected per protocol.

Controlling the Diabetic Body? Managing Chronic Illness with Wearable Technology.

I explore the experience of managing type 1 diabetes with wearable technology. Type 1 diabetes is a chronic illness which requires continuous maintenance to keep the blood glucose levels within range. Using autoethnography, I investigate both the practices of translating information from technology and from senses, and also from health authorities, into practices.

The SOS1 Inhibitor MRTX0902 Blocks KRAS Activation and Demonstrates Antitumor Activity in Cancers Dependent on KRAS Nucleotide Loading.

KRAS is the most frequently mutated oncogene in human cancer and facilitates uncontrolled growth through hyperactivation of the receptor tyrosine kinase (RTK)/mitogen-activated protein kinase (MAPK) pathway. The Son of Sevenless homolog 1 (SOS1) protein functions as a guanine nucleotide exchange factor (GEF) for the RAS subfamily of small GTPases and represents a druggable target in the pathway. Using a structure-based drug discovery approach, MRTX0902 was identified as a selective and potent SOS1 inhibitor that disrupts the KRAS:SOS1 protein-protein interaction to prevent SOS1-mediated nucleotide exchange on KRAS and translates into an anti-proliferative effect in cancer cell lines with genetic alterations of the KRAS-MAPK pathway.

Discovery of Pyridopyrimidinones that Selectively Inhibit the H1047R PI3Kα Mutant Protein.

The H1047R mutation of is highly prevalent in breast cancers and other solid tumors. Selectively targeting PI3Kα over PI3Kα is crucial due to the role that PI3Kα plays in normal cellular processes, including glucose homeostasis. Currently, only one PI3Kα-selective inhibitor has progressed into clinical trials, while three pan mutant (H1047R, H1047L, H1047Y, E542K, and E545K) selective PI3Kα inhibitors have also reached the clinical stage.