Challenging Situations in the Treatment of Cancer-Associated Thrombosis.

Cancer-associated thrombosis (CAT) is a common clinical problem in the treatment of cancer patients posing some unique challenges. These include the need to balance between the risk of recurrent thromboembolic events and bleeding complications in the individual cancer patient. A frequently encountered dilemma is the need for long-term anticoagulation in the setting of active malignancy.

Treatment-related survival patterns in diffuse intrinsic pontine glioma using a historical cohort: A report from the European Society for Pediatric Oncology DIPG/DMG Registry.

Background: Our aim is to investigate the association of treatment with survival in patients with diffuse intrinsic pontine glioma (DIPG) by examining 6 historical treatment paths.

Methods: We retrospectively analyzed data from 409 patients with radiologically centrally reviewed DIPG, sourced from the German Society of Pediatric Oncology and Hematology HIT-HGG trial database and the SIOPE-DIPG/DMG Registry. Survival outcomes were estimated using the Kaplan-Meier method, and univariable and multivariable Cox proportional hazard models were estimated to study treatment effects.

The impact of androgen-induced translation in modulating androgen receptor activity.

Introduction: Dysregulated androgen receptor (AR) activity is central to various diseases, particularly prostate cancer (PCa), in which it drives tumour initiation and progression. Consequently, antagonising AR activity via anti-androgens is an indispensable treatment option for metastatic PCa. However, despite initial tumour remission, drug resistance occurs.

Prognostic potential of standard laboratory parameters in patients with metastatic renal cell cancer receiving first-line immunotherapy.

Through their involvement in cancer metabolism, alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), γ-glutamyltransferase (GGT) and lactate dehydrogenase (LDH) reflect the tumor burden and thus could have a prognostic potential for patients treated with immune checkpoint inhibitors (CPI). Therefore, this study investigated the prognostic potential of these parameters in a real-world cohort of patients with metastatic renal cell cancer (mRCC) under first-line CPI-based therapy. The retrospective study cohort included 82 mRCC patients treated with CPI-based first-line therapy between 2019 and 2023.

Induction of circulating ABCB1 transcripts under platinum-based chemotherapy indicates poor prognosis and a bone micrometastatic phenotype in ovarian cancer patients.

The drug efflux transporter P-glycoprotein, encoded by the ABCB1 gene, promotes acquired chemoresistance. We explored the presence and clinical relevance of circulating cell-free ABCB1 transcripts (cfABCB1) in ovarian cancer patients (173 longitudinal serum samples from 79 cancer patients) using digital droplet PCR. cfABCB1 were readily detectable at primary diagnosis (median 354 mRNA copies/20 µl serum), paralleled FIGO-stage and predicted surgical outcome (p = 0.

Urinary-based detection of MSL, HE4 and CA125 as an additional dimension for predictive and prognostic modelling in ovarian cancer.

Objectives: We have recently described a predictive/prognostic model for ovarian cancer, exploiting commonly available clinico-pathological parameters and the ovarian serum biomarkers mesothelin (MSL), human epididymis protein 4 (HE4) and cancer-antigen 125 (CA125). Considering urine as a prototype non-invasive sample, we investigated whether serum levels of these biomarkers are mirrored in urine and compared their clinical relevance in matched serum urine samples.

Methods: MSL, HE4 and CA125 were quantified in urinary (n=172) and matched serum samples (n=188) from ovarian cancer patients (n=192) using the Lumipulse G chemiluminescent enzyme immunoassay (Fujirebio).

Emerging frontiers in androgen receptor research for prostate Cancer: insights from the 2nd international androgen receptor Symposium.

Continued exploration of the androgen receptor (AR) is crucial, as it plays pivotal roles in diverse diseases such as prostate cancer (PCa), serving as a significant therapeutic focus. Therefore, the Department of Urology Dresden hosted an international meeting for scientists and clinical oncologists to discuss the newest advances in AR research. The 2nd International Androgen Receptor Symposium was held in Dresden, Saxony, Germany, from 26-27.

Biomarker screen for efficacy of oncolytic virotherapy in patient-derived pancreatic cancer cultures.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a tumour entity with unmet medical need. To assess the therapeutic potential of oncolytic virotherapy (OVT) against PDAC, different oncolytic viruses (OVs) are currently investigated in clinical trials. However, systematic comparisons of these different OVs in terms of efficacy against PDAC and biomarkers predicting therapeutic response are lacking.

Type I conventional dendritic cells and CD8 T cells predict favorable clinical outcome of head and neck squamous cell carcinoma patients.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common tumor entities worldwide, with human papillomavirus (HPV) infection contributing to cancer development. Conventional therapies achieve only limited efficiency, especially in recurrent or metastatic HNSCC. As the immune landscape decisively impacts the survival of patients and treatment efficacy, this study comprehensively investigated the immunological tumor microenvironment (TME) and its association with patient outcome, with special focus on several dendritic cell (DC) and T lymphocyte subpopulations.

Attrition in the First Three Therapy Lines in Patients with Advanced Breast Cancer in the German Real-World PRAEGNANT Registry.

With more effective therapies for patients with advanced breast cancer (aBC), therapy sequences are becoming increasingly important. However, some patients might drop out of the treatment sequence due to deterioration of their life status. Since little is known about attrition in the real-world setting, this study assessed attrition in the first three therapy lines using a real-world registry.

Targeting the glutamine metabolism to suppress cell proliferation in mesenchymal docetaxel-resistant prostate cancer.

Docetaxel (DX) serves as a palliative treatment option for metastatic prostate cancer (PCa). Despite initial remission, acquired DX resistance is inevitable. The mechanisms behind DX resistance have not yet been deciphered, but a mesenchymal phenotype is associated with DX resistance.

Overcoming statin resistance in prostate cancer cells by targeting the 3-hydroxy-3-methylglutaryl-CoA-reductase.

Prostate cancer is the most prevalent malignancy in men. While diagnostic and therapeutic interventions have substantially improved in recent years, disease relapse, treatment resistance, and metastasis remain significant contributors to prostate cancer-related mortality. Therefore, novel therapeutic approaches are needed.

Tumour response to hypoxia: understanding the hypoxic tumour microenvironment to improve treatment outcome in solid tumours.

Hypoxia is a common feature of solid tumours affecting their biology and response to therapy. One of the main transcription factors activated by hypoxia is hypoxia-inducible factor (HIF), which regulates the expression of genes involved in various aspects of tumourigenesis including proliferative capacity, angiogenesis, immune evasion, metabolic reprogramming, extracellular matrix (ECM) remodelling, and cell migration. This can negatively impact patient outcomes by inducing therapeutic resistance.

Patient-Reported Outcomes in OlympiA: A Phase III, Randomized, Placebo-Controlled Trial of Adjuvant Olaparib in g Mutations and High-Risk Human Epidermal Growth Factor Receptor 2-Negative Early Breast Cancer.

Purpose: The OlympiA randomized phase III trial compared 1 year of olaparib (OL) or placebo (PL) as adjuvant therapy in patients with germline , high-risk human epidermal growth factor receptor 2-negative early breast cancer after completing (neo)adjuvant chemotherapy ([N]ACT), surgery, and radiotherapy. The patient-reported outcome primary hypothesis was that OL-treated patients may experience greater fatigue during treatment.

Methods: Data were collected before random assignment, and at 6, 12, 18, and 24 months.

New advances of the androgen receptor in prostate cancer: report from the 1st International Androgen Receptor Symposium.

The androgen receptor (AR) is a crucial player in various aspects of male reproduction and has been associated with the development and progression of prostate cancer (PCa). Therefore, the protein is the linchpin of current PCa therapies. Despite great research efforts, the AR signaling pathway has still not been deciphered, and the emergence of resistance is still the biggest problem in PCa treatment.

ALDH1A1 drives prostate cancer metastases and radioresistance by interplay with AR- and RAR-dependent transcription.

Current therapies for metastatic osseous disease frequently fail to provide a durable treatment response. To date, there are only limited therapeutic options for metastatic prostate cancer, the mechanisms that drive the survival of metastasis-initiating cells are poorly characterized, and reliable prognostic markers are missing. A high aldehyde dehydrogenase (ALDH) activity has been long considered a marker of cancer stem cells (CSC).

Cancer Stem Cells as a Therapeutic Target: Current Clinical Development and Future Prospective.

The key role of cancer stem cells (CSCs) in tumor development and therapy resistance makes them essential biomarkers and therapeutic targets. Numerous agents targeting CSCs, either as monotherapy or as part of combination therapy, are currently being tested in clinical trials to treat solid tumors and hematologic malignancies. Data from ongoing and future clinical trials testing novel approaches to target tumor stemness-related biomarkers and pathways may pave the way for further clinical development of CSC-targeted treatments and CSC-guided selection of therapeutic regimens.

Outcome after proton beam therapy versus photon-based radiation therapy in childhood-onset craniopharyngioma patients-results of KRANIOPHARYNGEOM 2007.

Background: Proton beam therapy (PBT) is being increas16ingly used to treat residual craniopharyngioma (CP) after hypothalamus-sparing surgery. Compared to photon-based radiation therapy (XRT) with PBT, less irradiation in the penumbra reduces the scattered dose to critical organs neighboring but outside the area of treatment, minimizing the risk of sequelae.

Patients And Methods: Between 2007 and 2019, 99 of 290 (34%) childhood-onset CP patients recruited in KRANIOPHARYNGEOM 2007 received external radiation therapy (RT) (65% PBT, 35% XRT).

CD98 heavy chain as a prognostic biomarker and target for cancer treatment.

The SLC3A2 gene encodes for a cell-surface transmembrane protein CD98hc (4F2). CD98hc serves as a chaperone for LAT1 (SLC7A5), LAT2 (SLC7A8), yLAT1 (SLC7A7), yLAT2 (SLC7A6), xCT (SLC7A11) and Asc1 (SLC7A10) providing their recruitment to the plasma membrane. Together with the light subunits, it constitutes heterodimeric transmembrane amino acid transporters.

A predictive and prognostic model for surgical outcome and prognosis in ovarian cancer computed by clinico-pathological and serological parameters (CA125, HE4, mesothelin).

Objectives: Numerous prognostic models have been proposed for ovarian cancer, extending from single serological factors to complex gene-expression signatures. Nonetheless, these models have not been routinely translated into clinical practice. We constructed a robust and readily calculable model for predicting surgical outcome and prognosis of ovarian cancer patients by exploiting commonly available clinico-pathological factors and three selected serum parameters.

RANK Expression as an Independent Predictor for Response to Neoadjuvant Chemotherapy in Luminal-Like Breast Cancer: A Translational Insight from the GeparX Trial.

Purpose: The GeparX study investigated whether denosumab as add-on treatment to nab-paclitaxel-based neoadjuvant chemotherapy (NACT) with two different schedules (125 mg/m² weekly vs. day 1, 8 every 22 days) may increase pathologic complete response (pCR) rate. The addition of denosumab to NACT did not improve pCR rates as recently published.

Early kinetics of C-reactive protein as prognosticator for survival in a real-world cohort of patients with metastatic renal cell cancer under first-line therapy with immune checkpoint inhibitors.

Purpose: This study investigated the prognostic potential of baseline C-reactive protein (CRP) levels and early CRP kinetics in a real-world cohort of patients with metastatic renal cell carcinoma (mRCC) under first-line (1L) therapy with immune checkpoint inhibitors (CPI).

Methods/patients: Analyses were performed retrospectively in a cohort of 61 mRCC patients under CPI-based 1L therapy. Patients were stratified based on baseline CRP (< 10 vs ≥ 10 mg/l) and CRP change within the initial three months of CPI therapy (normal: baseline < 10 mg/l, normalized: baseline ≥ 10 mg/l and nadir < 10 mg/l, non-normalized: baseline and nadir ≥ 10 mg/l).

Establishment and Molecular Characterization of an In Vitro Model for PARPi-Resistant Ovarian Cancer.

Overcoming PARPi resistance is a high clinical priority. We established and characterized comparative in vitro models of acquired PARPi resistance, derived from either a -proficient or -deficient isogenic background by long-term exposure to olaparib. While parental cell lines already exhibited a certain level of intrinsic activity of multidrug resistance (MDR) proteins, resulting PARPi-resistant cells from both models further converted toward MDR.