Targeting SWI/SNF Complexes in Cancer: Pharmacological Approaches and Implications.

SWI/SNF enzymes are heterogeneous multi-subunit complexes that utilize the energy from ATP hydrolysis to remodel chromatin structure, facilitating transcription, DNA replication, and repair. In mammalian cells, distinct sub-complexes, including cBAF, ncBAF, and PBAF exhibit varying subunit compositions and have different genomic functions. Alterations in the SWI/SNF complex and sub-complex functions are a prominent feature in cancer, making them attractive targets for therapeutic intervention. Current strategies in cancer therapeutics involve the use of pharmacological agents designed to bind and disrupt the activity of SWI/SNF complexes or specific sub-complexes. Inhibitors targeting the catalytic subunits, SMARCA4/2, and small molecules binding SWI/SNF bromodomains are the primary approaches for suppressing SWI/SNF function. Proteolysis-targeting chimeras (PROTACs) were generated by the covalent linkage of the bromodomain or ATPase-binding ligand to an E3 ligase-binding moiety. This engineered connection promotes the degradation of specific SWI/SNF subunits, enhancing and extending the impact of this pharmacological intervention in some cases. Extensive preclinical studies have underscored the therapeutic potential of these drugs across diverse cancer types. Encouragingly, some of these agents have progressed from preclinical research to clinical trials, indicating a promising stride toward the development of effective cancer therapeutics targeting SWI/SNF complex and sub-complex functions.

Physician Transition of Care: Benefits of I-PASS and an Electronic Handoff System in a Community Pediatric Residency Program.

BACKGROUND: Miscommunication is a leading cause of adverse events in hospitals. Optimizing the handoff process improves communication and patient safety. We sought to assess how the components of I-PASS (a mnemonic for illness severity, patient summary, action list, situational awareness with contingency planning, and synthesis by the receiver), a standardized handoff bundle, improved the quality of handoffs in a pediatric residency program based in a community hospital. METHODS: Pediatric residents in a university-affiliated community teaching hospital were observed on the pediatric inpatient floor and in the newborn nursery. One hundred resident handoffs per setting were analyzed in 3 phases, with a total of 600 handoffs assessed. Phase 1 comprised preintervention handoffs before I-PASS; phase 2, initiating I-PASS mnemonic and educational session; and phase 3, implementing a handoff tool, electronic physician handoff (EPH), into the electronic medical record. One attending physician at each setting assessed the handoff process using an 11-item survey. A resident satisfaction survey assessed the resident's experience after phase 3. RESULTS: Comparing phase 1 with phase 2, there was improved situational awareness with contingency planning (nursery: 12% to 83%, P = .001; floor: 21% to 84%, P = .001). Incidence of tangential conversation decreased in both settings (nursery: 100% to 23%, P = .001; floor: 84% to 11%, P = .001). Comparing phase 2 with phase 3, there was improvement in identification of illness severity (nursery: 62% to 99%, P = .001; floor: 41% to 64%, P = .001) and fewer omissions of important information (nursery: 14% to 0%, P = .001; floor: 33% to 17%, P = .007). A total of 93% of residents found the new EPH system to be beneficial. CONCLUSIONS: Specific components of a standardized handoff system, including a mnemonic, an educational intervention, and an EPH, improved the clarity and organization of key information in handoff.