Phase 1/2 trial of XPO1 inhibitor selinexor plus docetaxel in previously treated, advanced KRAS mutant non-small cell lung cancer.

Purpose: Patients with KRAS mutant non-small cell lung cancer (NSCLC) have limited therapeutic options. Based on activity of nuclear export inhibition in preclinical models, we evaluated this strategy in previously treated advanced KRAS mutant NSCLC.

Patients And Methods: The primary outcome of this multi-center phase 1/2 dose escalation trial of selinexor plus docetaxel was safety and tolerability.

Identification and Characterization of Avoidable Hospital Admissions in Patients With Lung Cancer.

Background: More than 50% of patients with lung cancer are admitted to the hospital while receiving treatment, which is a burden to patients and the healthcare system. This study characterizes the risk factors and outcomes of patients with lung cancer who were admitted to the hospital.

Methods: A multidisciplinary oncology care team conducted a retrospective medical record review of patients with lung cancer admitted in 2018.

Rural barriers and facilitators of lung cancer screening program implementation in the veterans health administration: a qualitative study.

Introduction: To assess healthcare professionals' perceptions of rural barriers and facilitators of lung cancer screening program implementation in a Veterans Health Administration (VHA) setting through a series of one-on-one interviews with healthcare team members.

Methods: Based on measures developed using Reach Effectiveness Adoption Implementation Maintenance (RE-AIM), we conducted a cross-sectional qualitative study consisting of one-on-one semi-structured telephone interviews with VHA healthcare team members at 10 Veterans Affairs medical centers (VAMCs) between December 2020 and September 2021. An iterative inductive and deductive approach was used for qualitative analysis of interview data, resulting in the development of a conceptual model to depict rural barriers and facilitators of lung cancer screening program implementation.

EGFR Kinase Domain Duplication (EGFR-KDD) Is a Novel Oncogenic Driver in Lung Cancer That Is Clinically Responsive to Afatinib.

Unlabelled: Oncogenic EGFR mutations are found in 10% to 35% of lung adenocarcinomas. Such mutations, which present most commonly as small in-frame deletions in exon 19 or point mutations in exon 21 (L858R), confer sensitivity to EGFR tyrosine kinase inhibitors (TKI). In analyzing the tumor from a 33-year-old male never-smoker, we identified a novel EGFR alteration in lung cancer: EGFR exon 18-25 kinase domain duplication (EGFR-KDD).

Mismatch repair-dependent iterative excision at irreparable O6-methylguanine lesions in human nuclear extracts.

The response of mammalian cells to Sn1 DNA methylators depends on functional MutSalpha and MutLalpha. Cells deficient in either of these activities are resistant to the cytotoxic effects of this class of chemotherapeutic drug. Because killing by Sn1 methylators has been attributed to O6-methylguanine (MeG), we have constructed nicked circular heteroduplexes that contain a single MeG-T mispair, and we have examined processing of these molecules by mismatch repair in nuclear extracts of human cells.

Inositol diphosphate signaling regulates telomere length.

Activation of phospholipase C-dependent inositol polyphosphate signaling pathways generates distinct messengers derived from inositol 1,4,5-trisphosphate that control gene expression and mRNA export. Here we report the regulation of telomere length by production of a diphosphorylinositol tetrakisphosphate, PP-IP4, synthesized by the KCS1 gene product. Loss of PP-IP4 production results in lengthening of telomeres, whereas overproduction leads to their shortening.