Publications by authors named "Hans-Georg Kopp"

Over 40% stage-III non-small-cell lung cancer (NSCLC) patients (pts) experience 5-year survival following multimodality treatment. Nevertheless, little is known about relevant late toxicities and quality-of-life (QoL) in the further long-term follow-up. Therefore, we invited pts from our randomized phase-III trial (Eberhardt et al.

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The Bcl-2 family controls apoptosis by direct interactions of pro- and anti-apoptotic proteins. The principle mechanism is binding of the BH3 domain of pro-apoptotic proteins to the hydrophobic groove of anti-apoptotic siblings, which is therapeutically exploited by approved BH3-mimetic anti-cancer drugs. Evidence suggests that also the transmembrane domain (TMD) of Bcl-2 proteins can mediate Bcl-2 interactions.

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Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) represent first-line standard of care in unresectable mutation-positive (m+) non-small cell lung cancer (NSCLC). However, 10-20% of patients with m+ NSCLC have uncommon variants, defined as mutations other than L858R substitutions or exon 19 deletions. NSCLC harboring uncommon mutations may demonstrate lower sensitivity to targeted agents than NSCLC with L858R or exon 19 deletion mutations.

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High-grade serous ovarian cancer (HGSOC) represents the most common and lethal subtype of ovarian cancer. Despite initial response to platinum-based standard therapy, patients commonly suffer from relapse that likely originates from drug-tolerant persister (DTP) cells. We generated isogenic clones of treatment-naïve and cisplatin-tolerant persister HGSOC cells.

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Article Synopsis
  • - Sotorasib, a KRAS p.G12C-inhibitor, was studied in real-world settings for patients with advanced non-small cell lung cancer (NSCLC) who had received prior treatments, revealing a 38.7% objective response rate and a median overall survival of 9.8 months.
  • - Data was collected from 163 patients in a compassionate use program, where a significant portion had poor performance status and existing brain metastases, and some required dose reductions or discontinuation.
  • - The study found that factors like PD-L1 expression and KEAP1 mutations influenced efficacy, with KEAP1 mutations associated with worse survival outcomes, while other mutations did not significantly affect response or survival.
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  • - Cancer-associated thrombosis (CAT) is a significant issue among lung cancer patients, increasing their risk of thrombosis compared to other cancers and potentially heightened by new treatments like immunotherapy and targeted therapies.
  • - Various risk-assessment models, such as the Khorana Risk Score, have been developed to evaluate thrombosis risk in lung cancer patients, considering factors like genetics and cancer stage.
  • - Management of CAT is guided by extensive trials showing effective use of anticoagulants like low-molecular-weight heparins and direct oral anticoagulants, with treatment tailored to individual patient factors and also impacted by the COVID-19 pandemic.
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  • The study investigates the effectiveness of chemotherapy (CHT) and immunotherapy (IO) in treating non-small cell lung cancer (NSCLC) with MET exon 14 skipping (METΔ14ex), involving 110 patients over six years in Germany.
  • Results indicate that combined CHT-IO treatment leads to better progression-free survival (PFS) and objective response rates compared to CHT alone, although overall survival (OS) was similar between CHT-IO and IO monotherapy.
  • Additionally, patients with TP53 mutations showed improved outcomes with treatment, while never-smokers were at a greater risk for primary progressive disease with IO.
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Objective: The EPAZ study (NCT01861951) showed recently that pazopanib was non-inferior to doxorubicin in patients ≥60 years treated in first line for advanced soft tissue sarcoma . The current post-hoc analysis aimed to assess the prognostic impact of frailty.

Methods: Geriatric assessments were evaluated at baseline.

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Background: Sequencing of tumour tissue with comprehensive gene panels is increasingly used to guide treatment in precision oncology. Analysis of tumour-normal pairs allows in contrast to tumour-only assessment direct discrimination between somatic and germline alterations, which might have important implications not only for the patients but also their families.

Methods: We performed tumour normal sequencing with a large gene panel in 1048 patients with advanced cancer to support treatment decision.

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Background: Despite advances in treatment of patients with non-small cell lung cancer, carriers of certain genetic alterations are prone to failure. One such factor frequently mutated, is the tumor suppressor PTEN. These tumors are supposed to be more resistant to radiation, chemo- and immunotherapy.

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Enhanced expression of anti-apoptotic B-cell lymphoma 2 (BCL-2) protein is frequent in cancer. Targeting of BCL-2 with the specific inhibitor ABT-199 (Venetoclax) has significant clinical activity in malignant diseases such as chronic lymphocytic leukemia and multiple myeloma. The small molecule drug ABT-199 mimics the pro-apoptotic BCL-2 homology domain 3 of BH3-only proteins and blocks the hydrophobic BC-groove in BCL-2.

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Immune-checkpoint inhibitors (ICI) have transformed oncological therapy. Up to 20% of all non-small cell lung cancers (NSCLCs) show durable responses upon treatment with ICI, however, robust markers to predict therapy response are missing. Here we show that blood platelets interact with lung cancer cells and that PD-L1 protein is transferred from tumor cells to platelets in a fibronectin 1, integrin α5β1 and GPIbα-dependent manner.

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Introduction: This exploratory analysis retrospectively evaluated outcomes in patients with advanced NSCLC to determine whether baseline brain metastases influenced the efficacy of first-line pembrolizumab plus chemotherapy versus chemotherapy alone.

Methods: We pooled data for patients with advanced NSCLC in KEYNOTE-021 cohort G (nonsquamous), KEYNOTE-189 (nonsquamous), and KEYNOTE-407 (squamous). Patients were assigned to platinum-doublet chemotherapy with or without the addition of 35 cycles of pembrolizumab 200 mg every 3 weeks.

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Background: Pemetrexed and cisplatin is a first-line standard in non-squamous non-small-cell lung cancer without targetable mutations. It became the backbone of checkpoint-inhibitor-chemotherapy combinations. Single high doses of cisplatin pose toxicity risks and require hyperhydration, potentially prolonging outpatient application.

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Soft tissue sarcoma (STS) constitutes a rare group of heterogeneous malignancies. Effective treatment options for most subtypes of STS are still limited. As a result, especially in metastatic disease, prognosis is still dismal.

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Importance: Pazopanib and gemcitabine have shown good tolerability, albeit modest single-agent activity in pretreated soft tissue sarcoma. A combined regimen to improve outcomes is required.

Objective: To determine the efficacy of gemcitabine and pazopanib compared with pazopanib alone.

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Sclerosing spindle cell rhabdomyosarcoma (SSRMS) is a rare rhabdomyosarcomas (RMS) subtype. Especially cases bearing a myogenic differentiation 1 () mutation are characterized by a high recurrence and metastasis rate, often leading to a fatal outcome. SSRMS cell lines are valuable in vitro models for studying disease mechanisms and for the preclinical evaluation of new therapeutic approaches.

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Regorafenib is a multi-target tyrosine kinase inhibitor that has been approved for the treatment of metastatic colorectal cancer, advanced hepatocellular carcinoma, and metastatic gastrointestinal stromal tumors (GIST). Severe hepatobiliary toxicity has been reported in patients with colorectal cancer treated with regorafenib, but not in those with GIST. Therefore, the aim of the present study was to investigate the incidence and clinical course of regorafenib-associated hepatic toxicity (HT) in patients with GIST in a real-world setting.

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Article Synopsis
  • * A small percentage of CLL patients (up to 5%) may experience a transformation to a more aggressive form called Richter's syndrome, which negatively impacts prognosis and is linked to decreased levels of NFAT2.
  • * The study reveals that targeting the tyrosine kinase LCK, a key regulator of NFAT2 in CLL, can disrupt the anergic state and reactivate BCR signaling, potentially speeding up the progression of CLL.
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Thrombocyte formation from megakaryocyte and their progenitor cells is tightly regulated by thrombopoietin (TPO) and its receptor c-MPL, thereby maintaining physiological functionality and numbers of circulating platelets. In patients, dysfunction of this regulation could cause thrombocytopenia or myeloproliferative syndromes. Since regulation of this pathway is still not completely understood, we investigated the role of the ubiquitin ligase c-Cbl which was previously shown to negatively regulated c-MPL signalling.

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Objectives: The choice of drug treatment in advanced soft tissue sarcoma (STS) continues to be a challenge regarding efficacy, quality of life (QoL) and toxicity. Unlike other cancer types, where integrating patient-reported outcomes (PRO) has proven to be beneficial for QoL, there is no such evidence in patients with STS as of now. The YonLife trial aimed to explore the effect of a tailored multistep intervention on QoL, symptoms and survival in patients with advanced STS undergoing treatment with trabectedin as well as identifying predictors of QoL.

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Purpose: Doxorubicin is a standard of care in patients with advanced, inoperable soft tissue sarcoma (STS). We tested whether pazopanib has efficacy comparable to that of doxorubicin in elderly patients with STS and offers superior tolerability for hematologic toxicity.

Patients And Methods: Patients age 60 years or older without previous systemic treatment for progressive advanced or metastatic STS who had Eastern Cooperative Oncology Group performance status of 0 to 2 and adequate organ function were included.

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Soft tissue sarcomas (STS) are a heterogeneous group of malignancies predominantly affecting children and young adults. Despite improvements in multimodal therapies, 5-year survival rates are only 50% and new treatment options in STS are urgently needed. To develop a rational combination therapy for the treatment of STS we focused on ABT-199 (Venetoclax), a BCL-2 specific BH3-mimetic, in combination with the proteasome inhibitor bortezomib (BZB).

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  • The study explores how LPS (lipopolysaccharide) can influence the development of neutrophils from stem cells when taken orally, without needing G-CSF (granulocyte colony-stimulating factor).
  • It establishes that TLR4 (Toll-like receptor 4) is essential for detecting LPS that affects neutrophil production in the body.
  • The findings highlight the importance of the gut microbiome in regulating neutrophil levels, which may be particularly relevant for patients undergoing chemotherapy or antibiotic treatment, as these therapies can alter the microbiome's structure.
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