Atlantic Cancer Research Institute

Public partnerships, engagement, and outreach are essential for meaningful knowledge dissemination and exchange activities in public settings. In 2024, we formed the Atlantic Cancer Consortium Patient Advisory Committee (ACC PAC). In March 2025, the ACC PAC delivered a successful public conference on precision medicine and cancer. Our primary objective is to share the perspectives gained, lessons learnt, impact of the event, and recommendations for future public conferences and engagement. Conference topics were identified by the ACC PAC. Speaker selection and conference promotion were done using various approaches and/or tools. The WebEx virtual platform was used to deliver the conference. This conference was open to all members of the public. A participant satisfaction survey was created using Qualtrics and distributed to registrants during and after the conference. Survey responses were summarized using descriptive statistics when appropriate. ACC PAC members who participated in the conference were encouraged to reflect on their experience. The ACC PAC patient advisors were involved in all key aspects of this conference's organization and delivery. A total of 24 speakers spoke during the conference on various cancer and patient-centered topics. Comments received and self-reflection exercise responses indicated a high level of impact and satisfaction associated with the content and delivery of the conference. Issues experienced, opportunities realized, and good practices implemented, as well as the feedback received helped us develop recommendations for improved delivery of future public conferences and better public engagement activities. In this Case Report, we discuss our learnings from a public conference that was designed and delivered by a public-scientist partnership. Overall, we were able to organize and deliver a successful public conference on precision medicine and cancer, yet there is still room for improvement in practical and technical areas. Our experience, self-reflection, and participant feedback that are described in this manuscript can help inform future public engagement and conference activities in Canada and beyond. Last, we ask decision-makers, such as governments, to provide sustained support for public partnerships and engagement in oncology.Public SummaryThe Atlantic Cancer Consortium Patient Advisory Committee (ACC PAC) is a patient - scientist partnership in Atlantic Canada focusing on precision medicine and cancer, advising the ACC researchers in research and public engagement activities, and actively working to engage with Atlantic Canadians in knowledge dissemination.This group organized and delivered a one-day public conference on March 15, 2025. Topics included patient and family perspectives, precision medicine, cancer risk factors and screening programs, support services offered to cancer-affected individuals, clinical trials, and advocacy. The conference was open to all members of the public. Overall, this was an impactful event centred on patient and family priorities, experiences, as well as on information and support needs.During and after the organization and delivery of this public event, we learnt by experience and from speaker and participant feedback. In this Case Report, we discuss these perspectives, lessons learnt, impact of the event, and recommendations for future public conferences. We also ask for sustained support and emphasis on public partnerships and engagement on cancer from decision-makers.

Background and Objectives:Next-generation sequencing (NGS) is transforming clinical diagnostics by enabling the detection of genetic variation with unprecedented precision. However, successful implementation of NGS workflows necessitates stringent quality control. This study introduces Molecular Genetics Dashboard (MGDB), a novel bioinformatics tool designed to enhance quality control in clinical NGS workflows.Methods:Using the Python dash framework for visualizations and MySQL databases, we have developed a novel tool for variant-level monitoring of clinical NGS sequencing runs. MGDB uses a docker-compose containerization for improved portability and can flexibly include or exclude samples from accumulated statistics with notes from interpreters.Results:MGDB facilitates variant-level run-to-run monitoring, ensuring the consistency of variant detection across sequencing cycles. The tool provides an interactive platform for visualizing and assessing variant data, identifying potential inconsistencies or outliers and improving data management and interpretation compared to traditional methods. MGDB was tested using samples sequenced with Oncomine Focus/Comprehensive Plus assays on S5 sequencers and analyzed via IonReporter software.Conclusions:MGDB offers a robust and user-friendly solution for enhancing quality control in clinical NGS workflows, contributing to greater accuracy and reliability in variant detection. The tool is freely available on GitHub: https://github.com/acri-nb/GeneticVariantsDB.

Glioblastoma (GBM) is a devastating universally fatal primary brain cancer. Novel therapeutic strategies are required to alter disease course and improve survival in these patients. There is increasing evidence that modulating cancer’s ability to respond to and survive cellular stress through RNA stress granules (SGs) may be a novel approach to cancer therapeutics. SGs are cytoplasmic aggregates of untranslated mRNAs and RNA binding proteins formed in response to a variety of cellular stressors, that allow cells to temporarily prioritize translation of stress-related proteins. A previous drug screen identified the dopamine modulator lobeline as a factor affecting SG disassembly in GBM cells. Lobeline impairs GBM cell survival by impairing SG disassembly after hypoxia. Specifically, after a hypoxic challenge, lobeline “locks” cells in a stressed state, even after re-exposure to normoxia. This is characterized by retained SGs, elevated levels of phosphorylated eIF2α and a sustained reduction in global protein translation. The disruption of the canonical stress response induced by lobeline ultimately results in increased cell death in both primary and immortalized GBM cell lines. Interestingly, lobeline also reduces post-hypoxia extracellular vesicle (EV) release, potentially through sequestration of the SG and EV protein, YBX1. Taken together, this adds to the literature that modulating stress and SG dynamics may be useful alone or to potentiate other treatment modalities affecting stress in GBM.

The introduction of immune checkpoint inhibitors (ICI) as first-line therapy in the treatment of non-small cell lung cancer has dramatically improved response rates. However, more than half of NSCLC patients receiving ICI fail to have a durable response to treatment and therefore the identification of circulating biomarkers to improve patient stratification is required. Cytokines and chemokines are critical mediators of immune responses, affecting tumor progression and immune evasion mechanisms. Thus, profiling circulating cytokines is particularly important, as these signaling molecules may provide valuable insights into predicting response and resistance to ICI. Twenty-four circulating chemokines and cytokines were profiled in NSCLC patient plasma collected either prior to treatment or while on-treatment with anti-PD1 therapy and correlated to treatment response as well as to progression-free survival (PFS) and overall survival (OS). Sex-disparities in correlations of cytokines to response and survival was analyzed. Regardless of sex, baseline levels of CCL5/RANTES were associated with anti-PD1 treatment response, while CXCL5 was associated with response in males and CXCL10 was elevated in female responders to anti-PD1 treatment. VEGF and CD40L were associated with short PFS and OS, while CCL5 and CXCL5 were correlated to longer PFS and OS. Sex disparities in baseline cytokine levels were also observed. CCL5 was significantly correlated to PFS and OS in females but not males, and CXCL10 was found to be predictive of longer OS in females only. VEGF was found to be a better predictor of response t to anti-PD1 in females, while CXCL12 was found to be associated with short PFS and OS in males but not females. Uniform Manifold Approximation and Projection (UMAP) dimension reduction method and k-means clustering analysis identified a cluster of male patients with short PFS characterized by elevated baseline levels of VEGF, CCL4, CCL5, CCL20, and CXCL2. Plasma cytokine levels can be useful biomarkers for predicting response to anti-PD1 therapy in NSCLC patients. However, the data presented in this study demonstrate that sex needs to be considered as an important variable in biomarker studies in immuno-oncology due to sex disparities in correlations of cytokines to anti-PD1 treatment response.

Abstract Background: High grade gliomas (HGGs) and cells of the tumour microenvironment (TME) secrete extracellular vesicles(EVs) into the plasma that contain genetic and protein cargo, which function in paracrine signaling. Isolation of these EVs and their cargo from plasma could lead to a simplistic tool that can inform on diagnosis and disease course of HGG. Methods: In the present study, plasma EVs were captured utilizing a peptide affinity method (Vn96 peptide) from HGG patients and normal controls followed by next generation sequencing (NovaSeq6000) to define a small RNA (sRNA) signature unique to HGG. Results: Over 750 differentially expressed sRNA (miRNA, snoRNA, lncRNA, tRNA, mRNA fragments and non-annotated regions) were identified between HGG and controls. MiEAA 2.0 pathway analysis of the miRNA in the sRNA signature revealed miRNA highly enriched in both EV and HGG pathways demonstrating the validity of results in capturing a signal from the TME. Also revealed were several novel HGG plasma EV sRNA biomarkers including lncRNA RPPH1 (Ribonuclease P Component H1), RNY4 (Ro60-Associated Y4) and RNY5 (Ro60-Associated Y5). Furthermore, in paired longitudinal patient plasma sampling, RPPH1 informed on surgical resection (decreased on resection) and importantly, RPPH1 increased again on clinically defined progression. Conclusions: The present study supports the role of plasma EV sRNA sampling (and particularly RPPH1) as part of a multi-pronged approach to HGG diagnosis and disease course surveillance.

We show that the transfer of foreign mitochondria by microparticles modulates recipient cancer cell metabolic plasticity, leading to greater malignant processes.

IntroductionAs the repercussions from the COVID-19 pandemic continue to unfold, an ever-expanding body of evidence suggests that infection also elicits pathophysiological manifestations within the central nervous system (CNS), known as neurological symptoms of post-acute sequelae of COVID infection (NeuroPASC). Although the neurological impairments and repercussions associated with NeuroPASC have been well described in the literature, its etiology remains to be fully characterized.ObjectivesThis mini-review explores the current literature that elucidates various mechanisms underlining NeuroPASC, its players, and regulators, leading to persistent neuroinflammation of affected individuals. Specifically, we provide some insights into the various roles played by microglial and astroglial cell reactivity in NeuroPASC and how these cell subsets potentially contribute to neurological impairment in response to the direct or indirect mechanisms of CNS injury.DiscussionA better understanding of the mechanisms and biomarkers associated with this maladaptive neuroimmune response will thus provide better diagnostic strategies for NeuroPASC and reveal new potential mechanisms for therapeutic intervention. Altogether, the elucidation of NeuroPASC pathogenesis will improve patient outcomes and mitigate the socioeconomic burden of this syndrome.

It is well established that inflammation and platelets promote multiple processes of cancer malignancy. Recently, platelets have received attention for their role in carcinogenesis through the production of microvesicles or platelet-derived microparticles (PMPs), which transfer their biological content to cancer cells. We have previously characterized a new subpopulation of these microparticles (termed mito-microparticles), which package functional mitochondria. The potential of mitochondria transfer to cancer cells is particularly impactful as many aspects of mitochondrial biology (i.e., cell growth, apoptosis inhibition, and drug resistance) coincide with cancer hallmarks and disease progression. These metabolic aspects are particularly notable in chronic lymphocytic leukemia (CLL), which is characterized by a relentless accumulation of proliferating, immunologically dysfunctional, mature B-lymphocytes that fail to undergo apoptosis. The present study aimed to investigate the role of PMPs on CLL metabolic plasticity leading to cancer cell phenotypic changes. CLL cell lines were co-incubated with different concentrations of human PMPs, and their impact on cell proliferation, mitochondrial DNA copy number, OCR level, ATP production, and ROS content was evaluated. Essential genes involved in metabolic-reprogramming were identified using the bioinformatics tools, examined between patients with early and advanced CLL stages, and then validated in PMP-recipient CLLs. Finally, the impact of the induced metabolic reprogramming on CLLs' growth, survival, mobility, and invasiveness was tested against anti-cancer drugs Cytarabine, Venetoclax, and Plumbagin. The data demonstrated the potency of PMPs in inducing tumoral growth and invasiveness in CLLs through mitochondrial internalization and OXPHOS stimulation which was in line with metabolic shift reported in CLL patients from early to advanced stages. This metabolic rewiring also improved CLL cells' resistance to Cytarabine, Venetoclax, and Plumbagin chemo drugs. Altogether, these findings depict a new platelet-mediated pathway of cancer pathogenesis. We also highlight the impact of PMPs in CLL metabolic reprogramming and disease progression.

For a long time, lysosomes were considered as mere waste bags for cellular constituents. Thankfully, studies carried out in the past 15 years were brimming with elegant and crucial breakthroughs in lysosome research, uncovering their complex roles as nutrient sensors and characterizing them as crucial multifaceted signaling organelles. This review presents the scientific knowledge on lysosome physiology and functions, starting with their discovery and reviewing up to date ground-breaking discoveries highlighting their heterogeneous functions as well as pending questions that remain to be answered. We also review the roles of lysosomes in anti-cancer drug resistance and how they undergo a series of molecular and functional changes during malignant transformation which lead to tumor aggression, angiogenesis, and metastases. Finally, we discuss the strategy of targeting lysosomes in cancer which could lead to the development of new and effective targeted therapies.