CK2 genes are overexpressed in many human cancers, and most often overexpression is associated with worse prognosis. Site-specific expression in mice leads to cancer development (e.g., breast, lymphoma) indicating the oncogenic nature of CK2. CK2 is involved in many key aspects of cancer including inhibition of apoptosis, modulation of signaling pathways, DNA damage response, and cell cycle regulation. A number of CK2 inhibitors are now available and have been shown to have activity against various cancers in vitro and in pre-clinical models. Some of these inhibitors are now undergoing exploration in clinical trials as well. In this review, we will examine some of the major cancers in which CK2 inhibition has promise based on in vitro and pre-clinical studies, the proposed cellular and signaling mechanisms of anti-cancer activity by CK2 inhibitors, and the current or recent clinical trials using CK2 inhibitors.

Monkeypox (MPX) is a zoonotic disease caused by the monkeypox virus (MPXV), belonging to the orthopoxvirus genus with a presentation resembling smallpox making it historically challenging to distinguish the disease from smallpox clinically. Since a British citizen brought MPX into the country on 6 May 2022, there have been concerns about the re-emergence of the human MPXV. Since then, the WHO has reported 92 confirmed cases and 28 suspected cases in 13 nations where MPXV was not endemic. WHO declared MPX a ‘public health emergency of international concern’ on 23 July 2022. MPXV can spread either through human-human contact or animal-human contact. Respiratory droplets, direct contact with bodily fluids, contaminated patient surroundings or objects, and skin sores from an infected person have all been linked to the disease’s transmission from one person to another. Fever, headache, lethargy, asthenia, enlargement of the lymph nodes, weariness, back pain, and myalgia are some of the symptoms that last from 2 to 5 weeks. It can be diagnosed using a range of diagnostic methods, including electron microscopy, Immunoglobulin M, enzyme-linked immunosorbent assay, polymerase chain reactions, histological analysis, immunofluorescent antibody testing, virus isolation, etc. Smallpox immunization before infection may lessen clinical symptoms and is around 85% effective in protecting from the MPXV.

Background: Mortality from non-small cell lung cancer (NSCLC) has improved with screening and novel treatments. The substance use epidemic has threatened health outcomes in a variety of diseases, but little is known about how it is associated with NSCLC outcomes. Methods:We performed a retrospective cohort study of 211 patients with NSCLC treated at a safetynet hospital. Sociodemographic data and clinical outcomes were extracted via review of electronic medical records. Patients were stratified based on substance use status. Comparative and multivariable analyses were performed to evaluate baseline characteristics and lung cancer outcomes including survival.Results: Among 193 patients (91.5%) with information available on substance use, 24.9% reported substance use; specifically, alcohol, marijuana, and illicit substances. Patients with substance use were more likely to have increased health care utilization and poor social determinants of health, including safe housing, stable employment, and social support. There were no significant differences in treatment adherence. Only 6.3% of patients with substance use did not receive guideline concordant care (GCC) compared to 24.8% of patients without substance use; due to poor performance status, increased comorbidities, or loss to follow up.On univariable analysis, patients with substance use experienced inferior median overall survival (OS) if they had metastatic disease (0.40 vs. 1.03 years, P=0.01). However, in the multivariable analysis, substance use did not predict for survival. Independent predictors of mortality were sex (male HR, 1.67; 95% CI: 1.04-2.68; P=0.04), smoking status (current smoking HR, 2.63; 95% CI: 1.14-6.08; P=0.02), and stage (stage IV HR, 14.96; 95% CI: 6.28-35.63; P=0.008).Conclusions: Substance use is associated with poor social determinants of health and increased health care utilization. On multivariable analysis, substance use was not independently associated with OS once guideline-concordant care was used. Future studies should focus on improving our understanding of these associations, delineating potential mechanisms, and developing evidence-based strategies to reduce health care utilization and overcome challenges related to poor social determinants of health.

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11545 Background: Frailty is a well-established predictor of survival, but assessing it in a real-world healthcare setting is often time-consuming and impractical. We sought to determine if a quantitative measure of frailty, computed automatically from electronic health records using the cumulative deficit model, also predicts overall survival in patients with NSCLC. Methods: We conducted a retrospective cohort study of Veterans identified to have NSCLC in the VA Precision Oncology Data Repository. Frailty was assessed using a previously validated FI, the Frailty Index for Veterans Affairs (VA-FI), consisting of 31 deficits. We categorized non-frail patients into non-frail (0-0.1) and pre-frail (0.1-0.2) groups, and frail patients into mild (0.2-0.3), moderate (0.3-0.4) and severe ( > 0.4) groups. Associations of frailty and survival were assessed using Kaplan-Meier estimates and Cox models. The added value of frailty status for predictive performance was quantified using the continuous net-reclassification index (NRI). Results: The cohort included 359 patients with NSCLC. The mean age was 66 years, and 96.1% were male, including 76.3% Caucasian and 16.2% African-American. The majority had an advanced stage cancer (15.9% and 44.3% with stages III and IV respectively) with minority falling into the early stage category (15.3% and 6.1% with stages I and II respectively). A substantial proportion of patients were identified to be frail (30%). The frailty categories differentiated survival profiles of patients with 2-year survival ranging from 0.41 for non-frail patients to 0.08 for the severely frail patients (log-rank p < 0.001). Frail patients exhibited significantly shorter survival than non-frail group even after adjusting for age, gender, and stage in a multivariate Cox model (hazard ratio 1.7, p < 0.001). Inclusion of frailty status in the Cox model significantly improved 2-year risk estimates of survival (NRI 0.35; 95% CI 0.27–0.47). Conclusions: Frailty as determined by VA-FI is a significant predictor of survival independent of stage and demographic factors among NSCLC patients in this VA cohort. VA-FI is an automated and a practically feasible tool to better estimate life expectancy and help individualize patient care.