Association between somatic microsatellite instability, hypermutation status, and specific T cell subsets in colorectal cancer tumors.

Background: Microsatellite instability-high (MSI-high) tumors comprise ~15% of sporadic colorectal cancers (CRC) and are associated with elevated T cell infiltration. However, the universality of this response across T cell subtypes with distinct functions is unknown.

Methods: Including 1,236 CRC tumors from three observational studies, we conducted T cell profiling using a customized 9-plex (CD3, CD4, CD8, CD45RA, CD45RO, FOXP3, KRT, MKI67, and DAPI) multispectral immunofluorescence assay.

Joint EANM/EANO/RANO/SNMMI practice guideline/procedure standard for PET imaging of brain metastases: version 1.0.

This joint practice guideline/procedure standard was collaboratively developed by the European Association of Nuclear Medicine (EANM), the Society of Nuclear Medicine and Molecular Imaging (SNMMI), the European Association of Neuro-Oncology (EANO), and the PET task force of the Response Assessment in Neurooncology Working Group (PET/RANO). Brain metastases are the most common malignant central nervous system (CNS) tumors. PET imaging with radiolabeled amino acids and to lesser extent [F]FDG has gained considerable importance in the assessment of brain metastases, especially for the differential diagnosis between recurrent metastases and treatment-related changes which remains a limitation using conventional MRI.

Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

Molecular Testing for the World Health Organization Classification of Central Nervous System Tumors: A Review.

Importance: Molecular techniques, including next-generation sequencing, genomic copy number profiling, fusion transcript detection, and genomic DNA methylation arrays, are now indispensable tools for the workup of central nervous system (CNS) tumors. Yet there remains a great deal of heterogeneity in using such biomarker testing across institutions and hospital systems. This is in large part because there is a persistent reluctance among third-party payers to cover molecular testing.

Feasibility of an electronic patient-facing cancer family history tool in medically underserved populations.

Purpose: We developed an electronic patient-facing family history collection tool including B-RST 3.0, PREMM risk assessments and "limited family knowledge/structure" information designed for primary care settings. We evaluated the tool's performance compared with genetic-counselor-collected information for clinical risk stratification in a population with barriers to access.

A chromosome-level reference genome for the common bed bug, Cimex lectularius, with identification of sex chromosomes.

The common bed bug, Cimex lectularius, is a globally distributed pest insect of medical, veterinary, and economic importance. Previous reference genome assemblies for this species were generated from short read sequencing data, resulting in a ~650 Mb composed of thousands of contigs. Here, we present a haplotype-resolved, chromosome-level reference genome, generated from an adult Harlen strain female specimen.

Deciphering the Tumor Microenvironment in Prostate Cancer: A Focus on the Stromal Component.

Prostate cancer progression is significantly affected by its tumor microenvironment, in which mesenchymal cells play a crucial role. Stromal cells are modified by cancer mutations, response to androgens, and lineage plasticity, and in turn, engage with epithelial tumor cells via a complex array of signaling pathways and ligand-receptor interactions, ultimately affecting tumor growth, immune interaction, and response to therapy. The metabolic rewiring and interplay in the microenvironment play an additional role in affecting the growth and progression of prostate cancer.

Development and validation of a clinical risk model for postoperative outcome in newly diagnosed glioblastoma: a report of the RANO resect group.

Background: Following surgery, patients with newly diagnosed glioblastoma frequently enter clinical trials. Nuanced risk assessment is warranted to reduce imbalances between study arms. Here, we aimed (I) to analyze the interactive effects of residual tumor with clinical and molecular factors on outcome and (II) to define a postoperative risk assessment tool.

Obesity-dependent selection of driver mutations in cancer.

Obesity is a risk factor for cancer, but whether obesity is linked to specific genomic subtypes of cancer is unknown. We examined the relationship between obesity and tumor genotype in two clinicogenomic corpora. Obesity was associated with specific driver mutations in lung adenocarcinoma, endometrial carcinoma and cancers of unknown primaries, independent of clinical covariates, demographic factors and genetic ancestry.

The present and future of the Cancer Dependency Map.

Despite tremendous progress in the past decade, the complex and heterogeneous nature of cancer complicates efforts to identify new therapies and therapeutic combinations that achieve durable responses in most patients. Further advances in cancer therapy will rely, in part, on the development of targeted therapeutics matched with the genetic and molecular characteristics of cancer. The Cancer Dependency Map (DepMap) is a large-scale data repository and research platform, aiming to systematically reveal the landscape of cancer vulnerabilities in thousands of genetically and molecularly annotated cancer models.

Germline DNA Damage Repair Variants and Prognosis of Patients with High-Risk or Metastatic Prostate Cancer.

Purpose: Deleterious germline variants in certain DNA repair genes are risk factors for developing aggressive prostate cancer. The objective was to quantify their prognostic impact after prostate cancer diagnosis.

Experimental Design: Men with prostate cancer, predominantly of European ancestry, were included from four cohorts with long-term follow-up.

Central nervous system tumors in adolescents and young adults: A Society for Neuro-Oncology consensus review on diagnosis, management, and future directions.

Adolescents and young adults (AYAs; ages 15-39 years) are a vulnerable population facing challenges in oncological care, including access to specialized care, transition of care, unique tumor biology, and poor representation in clinical trials. Brain tumors are the second most common tumor type in AYA, with malignant brain tumors being the most common cause of cancer-related death. The 2021 WHO Classification for central nervous system (CNS) Tumors highlights the importance of integrated molecular characterization with histologic diagnosis in several tumors relevant to the AYA population.

Novel Corrector for Variants of SLC6A8: A Therapeutic Opportunity for Creatine Transporter Deficiency.

Mutations in creatine transporter SLC6A8 cause creatine transporter deficiency (CTD), which is responsible for 2% of all cases of X-linked intellectual disability. CTD has no current treatments and has a high unmet medical need. Inspired by the transformational therapeutic impact of small molecule "correctors" for the treatment of cystic fibrosis, which bind to mutated versions of the CFTR ion channel to promote its trafficking to the cell surface, we sought to identify small molecules that could stabilize SLC6A8 as a potential treatment for CTD.

Updated EANO guideline on rational molecular testing of gliomas, glioneuronal, and neuronal tumors in adults for targeted therapy selection - Update 1.

The standard of care for adult patients with gliomas, glioneuronal and neuronal tumors consists of combinations of surgery, radiotherapy, and chemotherapy. For many systemic cancers, targeted treatments are a major part of the standard treatment, however, the predictive significance of most of the targets for treatment in systemic cancer are less well established in central nervous system (CNS) tumors . In 2023 the EANO Guideline Committee presented evidence based recommendations for rational testing of molecular targets for targeted treatments.

Design and conduct of theranostic trials in neuro-oncology: Challenges and opportunities.

Theranostics is a new treatment modality integrating molecular imaging with targeted radionuclide therapy. Theranostic agents have received regulatory approval for some systemic cancers and have therapeutic potential in neuro-oncology. As clinical trials are developed to evaluate the efficacy of theranostic agents in brain tumors, specific considerations will have to be considered, taking into account lessons learned from previous studies examining other treatment modalities in neuro-oncology.