Contributing Factors to the Rise in Adolescent Anxiety and Associated Mental Health Disorders: A Narrative Review of Current Literature.

Background: The prevalence of anxiety among adolescents has seen a notable increase in recent years, becoming a significant public health concern. In fact, anxiety is substantially more prevalent in Generation Z (individuals born between 1997 and 2012) than in any of the past three generations. We aimed to examine what factors contribute to the increased prevalence in teen anxiety and identify points of intervention.

Vertical Pathway Inhibition Overcomes Adaptive Feedback Resistance to KRAS Inhibition.

Purpose: Although represents the most commonly mutated oncogene, it has long been considered an "undruggable" target. Novel covalent inhibitors selective for the KRAS mutation offer the unprecedented opportunity to target KRAS directly. However, prior efforts to target the RAS-MAPK pathway have been hampered by adaptive feedback, which drives pathway reactivation and resistance.

Convergent Therapeutic Strategies to Overcome the Heterogeneity of Acquired Resistance in Colorectal Cancer.

Clonal heterogeneity associated with acquired resistance presents a critical therapeutic challenge. Whole-exome sequencing of paired tumor biopsies and targeted sequencing of cell-free DNA (cfDNA) from patients with colorectal cancer receiving BRAF inhibitor combinations identified 14 distinct alterations in MAPK pathway components driving acquired resistance, with as many as eight alterations in a single patient. We developed a pooled clone system to study clonal outgrowth during acquired resistance, and , the dynamics of individual resistant clones could be monitored in real time in cfDNA isolated from culture media during therapy.