Results of a patient-level pooled analysis of three studies of trastuzumab deruxtecan in HER2-positive breast cancer with active brain metastasis.

Background: Brain metastases (BMs) are common in human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer, increasing morbidity and mortality. Systemic therapy for BMs can be effective, with the triple combination of trastuzumab, capecitabine, and tucatinib being a potential standard. More recently, intracranial activity of antibody-drug conjugates has been reported, but the size of individual studies has been small.

Emergence of immune-related adverse events correlates with pathological complete response in patients receiving pembrolizumab for early triple-negative breast cancer.

Based upon results of the KEYNOTE-522 trial and following approval by regulatory authorities, the addition of pembrolizumab to chemotherapy is now the standard-of-care for the treatment of early triple-negative breast cancer (eTNBC) (Clinical stage II-III). Pembrolizumab is a programmed cell death protein 1 monoclonal antibody, known to cause immune-related adverse events (irAEs) in a significant subset of patients. Real-world data on incidence, type and treatment strategies of irAEs in the setting of eTNBC treatment are sparse.

Comparison of RNA Marker Panels for Circulating Tumor Cells and Evaluation of Their Prognostic Relevance in Breast Cancer.

Liquid biopsy is a promising tool for therapy monitoring of cancer patients, but a need for further research in this field exists in order to improve sensitivity, specificity, standardization and minimize costs. In our present study, we evaluated two panels of transcripts related with the presence of circulating tumor cells (CTCs) (Panel 1: , , and Panel 2: , , , , and ) in two cohorts of breast cancer patients (metastatic and early). A blood cell fraction possibly containing CTCs was isolated with density gradient centrifugation, followed by RNA isolation and qPCR using TaqMan or RT-qPCR using hybridization probes.

Influence of HER2 expression on prognosis in metastatic triple-negative breast cancer-results from an international, multicenter analysis coordinated by the AGMT Study Group.

Background: Triple-negative breast cancer (TNBC) is associated with poor prognosis, and new treatment options are urgently needed. About 34%-39% of primary TNBCs show a low expression of human epidermal growth factor receptor 2 (HER2-low), which is a target for new anti-HER2 drugs. However, little is known about the frequency and the prognostic value of HER2-low in metastatic TNBC.

Atezolizumab plus nab-paclitaxel for unresectable, locally advanced or metastatic breast cancer: real-world results from a single academic center in Austria.

Purpose: IMpassion130 led to the approval of atezolizumab plus nab-paclitaxel as first-line treatment for patients with unresectable locally advanced or metastatic triple-negative, PD-L1 immune-cell positive breast cancer (BC) by the European Medicines Agency (EMA). The objective of the present study was to investigate the implementation, safety and efficacy of this combination in the initial phase after approval.

Methods: A retrospective data analysis including all BC patients who received atezolizumab and nab-paclitaxel between 1.

MALAT1 Fusions and Basal Cells Contribute to Primary Resistance against Androgen Receptor Inhibition in TRAMP Mice.

Targeting testosterone signaling through androgen deprivation therapy (ADT) or antiandrogen treatment is the standard of care for advanced prostate cancer (PCa). Although the large majority of patients initially respond to ADT and/or androgen receptor (AR) blockade, most patients suffering from advanced PCa will experience disease progression. We sought to investigate drivers of primary resistance against antiandrogen treatment in the TRAMP mouse model, an SV-40 t-antigen driven model exhibiting aggressive variants of prostate cancer, castration resistance, and neuroendocrine differentiation upon antihormonal treatment.

The prostate cancer landscape in Europe: Current challenges, future opportunities.

Prostate cancer (PCa) is the most common non-cutaneous cancer in men in Europe and is predicted to exhibit declining mortality in the European Union (EU) due to various recent improvements in treatment. The goal of this short review is to give insight into the European treatment landscape of PCa, while focusing on improvements in care.

A Data Integration Workflow to Identify Drug Combinations Targeting Synthetic Lethal Interactions.

A synthetic lethal interaction between two genes is given when knock-out of either one of the two genes does not affect cell viability but knock-out of both synthetic lethal interactors leads to loss of cell viability or cell death. The best studied synthetic lethal interaction is between BRCA1/2 and PARP1, with PARP1 inhibitors being used in clinical practice to treat patients with BRCA1/2 mutated tumors. Large genetic screens in model organisms but also in haploid human cell lines have led to the identification of numerous additional synthetic lethal interaction pairs, all being potential targets of interest in the development of novel tumor therapies.

Loss of HCRP1 leads to upregulation of PD-L1 via STAT3 activation and is of prognostic significance in EGFR-dependent cancer.

Loss of hepatocellular carcinoma-related protein 1 (HCRP1) (alias VPS37A) plays a role in endocytosis of receptor tyrosine kinases as a member of the ESCRT complex and has been linked to poor patient outcome in various types of epithelial cancer. To this date, the molecular and biological mechanisms explaining how its absence would contribute to tumor progression remain unknown. Using genomic editing with CRISPR-Cas9, we generated ovarian and breast cancer cell lines with loss-of-function mutations of HCRP1.

Thirteen-year analyses of medical oncology outpatient day clinic data: a changing field.

Background: Novel treatment modalities like targeted therapy and immunotherapy are currently changing treatment strategies and protocols in the field of medical oncology.

Methods: Numbers of patients and patient contacts admitted to medical oncology day clinics of a large European academic cancer centre in the period from 2006 to 2018 were analysed using our patient administration system.

Results: A patient cohort of 9.

Assessment of body composition in the advanced stage of castration-resistant prostate cancer: special focus on sarcopenia.

Purpose: To assess the prevalence of sarcopenia and whether body composition parameters are associated with disease progression and overall survival (OS) in castration-resistant prostate cancer (CRPC) patients.

Materials And Methods: This single-centre retrospective study evaluated data of 186 consecutive patients who underwent chemohormonal therapy between 2005 and 2016 as first-line systemic treatment for CRPC. Skeletal muscle and fat indices were determined using computerized tomography data before initiation of chemotherapy.

Immune checkpoint inhibitors in mCRPC - rationales, challenges and perspectives.

The advancement of immune-therapeutics in cancer treatment has proven to be promising in various malignant diseases. However, in castration resistant prostate cancer (mCRPC) major Phase III trials have been unexpectedly disappointing. To contribute to a broader understanding of the role and use of immune-therapeutics in mCRPC, we conducted a systematic review.

Synthetic lethality guiding selection of drug combinations in ovarian cancer.

Background: Synthetic lethality describes a relationship between two genes where single loss of either gene does not trigger significant impact on cell viability, but simultaneous loss of both gene functions results in lethality. Targeting synthetic lethal interactions with drug combinations promises increased efficacy in tumor therapy.

Materials And Methods: We established a set of synthetic lethal interactions using publicly available data from yeast screens which were mapped to their respective human orthologs using information from orthology databases.

Effects of resistance exercise in prostate cancer patients: a meta-analysis.

Purpose: The aim of the present meta-analysis was to quantify effects of resistance exercise (RE) on physical performance and function, body composition, health-related quality of life (HRQoL), and fatigue in patients with prostate cancer.

Methods: Trial data were obtained from the databases PubMed, MEDLINE, EMBASE, SCOPUS, and the Cochrane Library as of inception to 31st of December 2016. Thirty-two trials with 1199 patients were included.

SPAG6 and L1TD1 are transcriptionally regulated by DNA methylation in non-small cell lung cancers.

Background: DNA methylation regulates together with other epigenetic mechanisms the transcriptional activity of genes and is involved in the pathogenesis of malignant diseases including lung cancer. In non-small cell lung cancer (NSCLC) various tumor suppressor genes are already known to be tumor-specifically methylated. However, from the vast majority of a large number of genes which were identified to be tumor-specifically methylated, tumor-specific methylation was unknown so far.

Recent developments and translational aspects in targeted therapy for metastatic breast cancer.

Biologically distinct subtypes of metastatic breast cancer (MBC) have been defined by multiple efforts in recent years, showing broad heterogeneity at the molecular level of disease. Throughout this endeavour, oncogenic drivers within MBC were identified as potential therapeutic targets. With recent results from clinical trials targeting these well-known cancer-promoting pathways, this review is trying to elucidate as well as summarise current new therapeutic aspects in MBC and shed light on translational aspects within this entity.