Datopotamab Deruxtecan in Advanced or Metastatic Non-Small Cell Lung Cancer With Actionable Genomic Alterations: Results From the Phase II TROPION-Lung05 Study.

Purpose: Datopotamab deruxtecan (Dato-DXd) is a trophoblast cell-surface antigen-2-directed antibody-drug conjugate with a highly potent topoisomerase I inhibitor payload. The TROPION-Lung05 phase II trial (ClinicalTrials.gov identifier: NCT04484142) evaluated the safety and clinical activity of Dato-DXd in patients with advanced/metastatic non-small cell lung cancer (NSCLC) with actionable genomic alterations progressing on or after targeted therapy and platinum-based chemotherapy.

Apocynaceae wood evolution matches key morphological innovations.

Premise: This paper provides an overview of the wood anatomy of the dogbane family (Apocynaceae), reconstructs wood anatomical trait evolution, and links this evolution with woody growth-form transitions and floral and seed trait innovations across the family.

Methods: Over 200 published wood anatomical descriptions were revised, and original light microscopic sections were made and described for another 50 species. Changes in wood anatomical characters through time were visualized with ancestral state reconstructions.

Patient characteristics, treatment patterns, and survival outcomes for patients with malignant pleural mesothelioma in Denmark between 2011 and 2018: a nationwide population-based cohort study.

Background: Malignant pleural mesothelioma (MPM) is a rare thoracic malignancy with poor prognosis and limited treatment options. Immunotherapy shows potential for improved outcomes; however, real-world evidence on its use will take time to accumulate. This study examined patient characteristics, treatment patterns, overall survival (OS), and predictors of mortality among patients diagnosed with MPM in Denmark prior to the introduction of newer treatments.

Immune checkpoint inhibition in early-stage non-small cell lung cancer.

The introduction of immune checkpoint inhibitors significantly advanced outcomes in both metastatic and locally advanced non-small cell lung cancer. Despite these advancements, the 5-year survival rate remains suboptimal. Even in early-stage disease a significant portion of patients relapse and die from metastatic progression.

Dendritic cells loaded with allogeneic tumour cell lysate plus best supportive care versus best supportive care alone in patients with pleural mesothelioma as maintenance therapy after chemotherapy (DENIM): a multicentre, open-label, randomised, phase 2/3 study.

Background: Dendritic cell immunotherapy has proven to be safe and induces an immune response in humans. We aimed to establish the efficacy of dendritic cells loaded with allogeneic tumour cell lysate (MesoPher, Amphera BV, 's-Hertogenbosch, Netherlands) as maintenance therapy in patients with pleural mesothelioma.

Methods: In this open-label, randomised, phase 2/3 study, patients with histologically confirmed unresectable pleural mesothelioma, aged 18 years or older, with an Eastern Cooperative Oncology Group performance status score of 0-1, and non-progressing disease after four to six cycles of standard chemotherapy (with pemetrexed 500 mg/m plus platinum [cisplatin 75 mg/m or carboplatin area under the curve of 5]) were recruited from four centres in Belgium, France, and The Netherlands.

A randomised phase II study of extended pleurectomy/decortication preceded or followed by chemotherapy in patients with early-stage pleural mesothelioma: EORTC 1205.

Background: The role of surgery in pleural mesothelioma remains controversial. It may be appropriate in highly selected patients as part of a multimodality treatment including chemotherapy. Recent years have seen a shift from extrapleural pleuropneumonectomy toward extended pleurectomy/decortication.

Neoadjuvant nivolumab with or without relatlimab in resectable non-small-cell lung cancer: a randomized phase 2 trial.

Antibodies targeting the immune checkpoint molecules PD-1, PD-L1 and CTLA-4, administered alone or in combination with chemotherapy, are the standard of care in most patients with metastatic non-small-cell lung cancers. When given before curative surgery, tumor responses and improved event-free survival are achieved. New antibody combinations may be more efficacious and tolerable.

Pembrolizumab plus lenvatinib in second-line and third-line patients with pleural mesothelioma (PEMMELA): a single-arm phase 2 study.

Background: The combination of pembrolizumab, an anti-PD-1 antibody, and lenvatinib, an antiangiogenic multikinase inhibitor, shows synergistic activity in preclinical and clinical studies in solid tumours. We assessed the clinical activity of this combination therapy in patients with pleural mesothelioma who progressed after platinum-pemetrexed chemotherapy.

Methods: In this single-arm, single-centre, phase 2 study, done at the Netherlands Cancer Institute in Amsterdam, The Netherlands, eligible patients (aged ≥18 years) with pleural mesothelioma with an Eastern Cooperative Oncology Group performance status of 0-1, progression after chemotherapy (no previous immunotherapy), and measurable disease according to the modified Response Evaluation Criteria In Solid Tumours (mRECIST) for mesothelioma version 1.

Dynamics and survival associations of T cell receptor clusters in patients with pleural mesothelioma treated with immunotherapy.

Background: Immune checkpoint inhibitors (ICIs) are now a first-line treatment option for patients with pleural mesothelioma with the recent approval of ipilimumab and nivolumab. Mesothelioma has a low tumor mutation burden and no robust predictors of survival with ICI. Since ICIs enable adaptive antitumor immune responses, we investigated T-cell receptor (TCR) associations with survival in participants from two clinical trials treated with ICI.

Veteran-derived cerebral organoids display multifaceted pathological defects in studies on Gulf War Illness.

Approximately 30% of the veterans who fought in the 1991 Gulf War (GW) suffer from a disease called Gulf War Illness (GWI), which encompasses a constellation of symptoms including cognitive deficits. A coalescence of evidence indicates that GWI was caused by low-level exposure to organophosphate pesticides and nerve agents in combination with physical stressors of the battlefield. Until recently, progress on mechanisms and therapy had been limited to rodent-based models.

IL-5-producing CD4 T cells and eosinophils cooperate to enhance response to immune checkpoint blockade in breast cancer.

Immune checkpoint blockade (ICB) has heralded a new era in cancer therapy. Research into the mechanisms underlying response to ICB has predominantly focused on T cells; however, effective immune responses require tightly regulated crosstalk between innate and adaptive immune cells. Here, we combine unbiased analysis of blood and tumors from metastatic breast cancer patients treated with ICB with mechanistic studies in mouse models of breast cancer.

Microtubule polarity flaws as a treatable driver of neurodegeneration.

Microtubule disruption is a common downstream mechanism leading to axonal degeneration in a number of neurological diseases. To date, most studies on this topic have focused on the loss of microtubule mass from the axon, as well as changes in the stability properties of the microtubules and/or their tubulin composition. Here we posit corruption of the normal pattern of microtubule polarity orientation as an underappreciated and yet treatable contributor to axonal degeneration.

Immune cells in mesothelioma microenvironment simplistic marker of response to nivolumab plus ipilimumab?

Introduction: Malignant pleural mesothelioma (MPM) is a malignant disease of the pleura which recently can be treated with immune checkpoint inhibitors (ICI). To optimize this treatment, a better understanding of the tumor micro environment is needed. We investigated subgroups of immune cells in subsequent tumor biopsies of patients treated with ICI.

Expression of phosphorylated ribosomal protein S6 in mesothelioma patients - correlation with clinico-pathological characteristics and outcome: results from the European Thoracic Oncology Platform (ETOP) Mesoscape project.

Pleural mesothelioma (PM) is an aggressive malignancy with poor prognosis. Although histology and pathologic stage are important prognostic factors, better prognostic biomarkers are needed. The ribosomal protein S6 is a downstream target of the phosphatidylinositol 3-kinase (PI3K) pathway involved in protein synthesis and cell proliferation.