Purpose-Religion and spirituality play a role in coping with illness for many cancer patients. This study examined religiousness and spiritual support in advanced cancer patients of diverse racial/ ethnic backgrounds and associations with quality of life (QOL), treatment preferences, and advance care planning. Methods-TheCoping With Cancer study is a federally funded, multi-institutional investigation examining factors associated with advanced cancer patient and caregiver well-being. Patients with an advanced cancer diagnosis and failure of first-line chemotherapy were interviewed at baseline regarding religiousness, spiritual support, QOL, treatment preferences, and advance care planning.Results-Most (88%) of the study population (N = 230) considered religion to be at least somewhat important. Nearly half (47%) reported that their spiritual needs were minimally or not at all supported by a religious community, and 72% reported that their spiritual needs were supported minimally or not at all by the medical system. Spiritual support by religious communities or the medical system was significantly associated with patient QOL (P = .0003). Religiousness was significantly associated with wanting all measures to extend life (odds ratio, 1.96; 95% CI, 1.08 to 3.57). Conclusion-Many

Epidermal growth factor receptor (EGFR) gene mutations (G719X, exon 19 deletions/insertions, L858R and L861Q) predict favorable responses to EGFR tyrosine kinase inhibitors (TKIs) in advanced non-small-cell lung cancer (NSCLC). However, EGFR exon 20 insertion mutations (∼10% of all EGFR mutations) are generally associated with insensitivity to available TKIs (gefitinib, erlotinib and afatinib). The basis of this primary resistance is poorly understood.  We study a broad subset of exon 20 insertion mutations, comparing in vitro TKI sensitivity with responses to gefitinib and erlotinib in NSCLC patients; and find that most are resistant to EGFR TKIs. The crystal structure of a representative TKI-insensitive mutant (D770_N771insNPG) reveals an unaltered ATP-binding pocket and the inserted residues form a wedge at the end of the C-helix that promotes the active kinase conformation. Unlike EGFR-L858R, D770_N771insNPG activates EGFR without increasing its affinity for EGFR TKIs. Unexpectedly, we find that EGFR-A763_Y764insFQEA is highly sensitive to EGFR TKIs in vitro; and patients whose NSCLCs harbor this mutation respond to erlotinib. Analysis of the A763_Y764insFQEA mutant indicates that the inserted residues shift the register of the C-helix in the N-terminal direction, altering the structure in the region that is also affected by the TKI-sensitive EGFR-L858R. Our studies reveal intricate differences between EGFR mutations, their biology and their response to EGFR TKIs.