Protein kinase CSNK2 (CK2) is a pleiotropic serine/threonine kinase frequently dysregulated in solid and hematologic malignancies. To consolidate a wide range of biological and clinically oriented data from this unique kinase in cancer, this systematic review summarises existing knowledge from in vitro, in vivo and pre-clinical studies on CSNK2 across 24 different human cancer types. CSNK2 mRNA transcripts, protein levels and activity were found to be routinely upregulated in cancer, and commonly identified phosphotargets included AKT, STAT3, RELA, PTEN and TP53. Phenotypically, it frequently influenced evasion of apoptosis, enhancement of proliferation, cell invasion/metastasis and cell cycle control. Clinically, it held prognostic significance across 14 different cancers, and its inhibition in xenograft experiments resulted in a positive treatment response in 12. In conjunction with commentary on preliminary studies of CSNK2 inhibitors in humans, this review harmonises an extensive body of CSNK2 data in cancer and reinforces its emergence as an attractive target for cancer therapy. Continuing to investigate CSNK2 will be crucial to advancing our understanding of CSNK2 biology, and offers the promise of important new discoveries scientifically and clinically.

The origins of cancer vaccines date back to the 1800s. Since then, there have been significant efforts to generate vaccines against solid and hematologic malignancies using a variety of platforms. To date, these efforts have generally been met with minimal success. However, in the era of improved methods and technological advancements, supported by compelling preclinical and clinical data, a wave of renewed interest in the field offers the promise of discovering field-changing paradigms in the management of established and resected disease using cancer vaccines. These include novel approaches to personalized neoantigen vaccine development, as well as innovative immune-modulatory vaccines (IMVs) that facilitate activation of antiregulatory T cells to limit immunosuppression caused by regulatory immune cells. This article will introduce some of the limitations that have affected cancer vaccine development over the past several decades, followed by an introduction to the latest advancements in neoantigen vaccine and IMV therapy, and then conclude with a discussion of some of the newest technologies and progress that are occurring across the cancer vaccine space. Cancer vaccines are among the most promising frontiers for breakthrough innovations and strategies poised to make a measurable impact in the ongoing fight against cancer.

Extracellular vesicles (EVs) are cell-derived nanoparticles that have attracted significant attention in the investigation of human health and disease, including cancer biology and its clinical management. Concerning cancer, EVs have been shown to influence numerous aspects of oncogenesis, including tumor proliferation and metastasis. EVs can augment the immune system and have been implicated in virtually all aspects of innate and adaptive immunity. With immunotherapy changing the landscape of cancer treatment across multiple disease sites, it is paramount to understand their mechanisms of action and to further improve upon their efficacy. Despite a rapidly growing body of evidence supporting of the utility of EVs in cancer diagnostics and therapeutics, their application in clinical trials involving solid tumors and immunotherapy remains limited. To date, relatively few trials are known to incorporate EVs in this context, mainly employing them as biomarkers. To help address this gap, this review summarizes known applications of EVs in clinical trials and provides a brief overview of the roles that EVs play in cancer biology, immunology, and their proposed implications in immunotherapy. The impetus to leverage EVs in future clinical trials and correlative studies is crucial, as they are ideally positioned to synergize with advancements in multi-omics research to further therapeutic discovery and our understanding of cancer biology.

Background: Cutaneous squamous cell carcinoma (cSCC) is the second most common nonmelanoma skin cancer in Canada. However, few real-world reports exist on the treatment of refractory locally advanced (LA) and metastatic cSCC with cemiplimab to date. Objectives: The objective of this study was to characterize the demographic and clinical outcomes of advanced cSCC patients on cemiplimab in a real-world setting. Methods: Retrospective analysis of adult patients with refractory LA and metastatic cSCC treated with cemiplimab at the London Regional Cancer Program in Canada. Patient demographics and treatment characteristics were reported, as well as Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS). Results: Forty patients were included in this study. Sixteen (40%) had LA disease and 24 (60%) had metastatic disease. Median treatment duration was 3.5 months (range: 0.6-29.4 months). Kaplan-Meier analyses of the entire study population revealed that the median OS was not reached [NR; 95% confidence interval (CI) 9.1 months-NR], but median PFS was 11.5 months (95% CI 7.0 months-NR). A total of 25% of patients experienced at least one adverse event from cemiplimab. Reasons for treatment discontinuation were death from any cause (25%), disease progression (15%), cemiplimab adverse events (5%), and other causes (15%). Discussion: The 12 month estimates of OS and PFS were lower than pivotal phase I and II clinical trials. However, toxicity was tolerable. Cemiplimab remains a safe and effective therapy in patients with refractory LA and metastatic cSCC disease.

Circulating tumor DNA (ctDNA) has many potential applications in the management of cancer, including detection, monitoring, and treatment response assessment. This study evaluates pre-treatment ctDNA detection in a single-institution pan-cancer cohort using a highly sensitive tumor-informed ctDNA assay. Participant samples were collected at the University Health Network across six study cohorts. A total of 273 patients with stage II-IV cancers spanning 16 tumor types were analyzed using a personalized tumor-informed assay (RaDaR^®). Harmonized methods were employed to mitigate the impact of variables known to influence ctDNA detection and its quantification. Pre-treatment ctDNA was detected in 83% of participants (226/273) across all stages and cancer types. Detection rates varied by clinical characteristics, including cancer type and stage; ctDNA was detected in 100% of stage IV metastatic recurrent high-grade serous ovarian cancer (HGSOC) patients (n = 8/8) and 54% of stage IV melanoma patients (n = 6/11). The median estimated variant allele fraction (eVAF) across all patients with a positive ctDNA result was 0.25% (range: 0.000029–37.7%), varied by tumor type and increased with cancer stage. A total of 11% of positive samples (24/226) had an eVAF of <0.01%. This pan-cancer ctDNA analysis using a highly sensitive assay reveals high detection rates overall, including ~10% at low levels (<0.01% eVAF), offering a reference for future clinical ctDNA applications and furthering our understanding of factors influencing ctDNA measurements.

Background. We describe a case report of a 67-year-old male with PDAC who experienced an exceptional survival outcome during systemic therapy and its implications in precision medicine. We hypothesize that his outcomes are attributable, in part, to a germline BRCA2 deletion and somatic GNAS substitution. Methods. Retrospective single-patient chart review was performed at the London Regional Cancer Program, as well as a structured literature search spanning all years in PubMed of BRCA and GNAS mutations in pancreatic cancer. Results. The case described herein represents a 67-year-old male who survived over 27 months after third-line treatment with gemcitabine, docetaxel, and capecitabine (GTX) chemotherapy for metastatic PDAC after progression on gemcitabine and Abraxane and then on FOLFIRINOX. His survival far exceeded the median overall survival metrics. Genetic testing revealed a pathogenic heterozygous germline BRCA2 6643delT p.(Tyr2215Thrfs14) frameshift mutation and somatic p.(Arg844His) mutation. Conclusions. This case highlights the urgent need to expand our knowledge of cancer biology to advance personalized cancer treatment and therapy development.