Introduction: Small cell transformation (SCT) is a typical mechanism of adaptive resistance to third generation epidermal growth factor receptor inhibitors (EGFRi) which have become the standard of care for EGFR-driven non-small cell lung cancer (EGFR+ NSCLC). Little is known about the optimal management of SCT patients. This study aimed to compare outcomes under platinum/etoposide chemotherapy alone (chemo) or in combination with EGFR inhibitors (EGFRi+chemo) or immune checkpoint inhibitors (ICI+chemo).
View Article and Find Full Text PDFMetastatic prostate cancer (mPCa) is a widespread disease with high mortality. Unraveling molecular mechanisms of disease progression is of utmost importance. The microenvironment in visceral organs and the skeletal system is of particular interest as a harbinger of metastatic spread.
View Article and Find Full Text PDFHydroxyurea is an antimetabolite that inhibits DNA synthesis and is used as a treatment option in chronic myeloproliferative disorders. Rarely, "dermatomyositis (DM)-like" skin lesions are observed after long-term therapy. In this case series, five skin biopsies of four patients were evaluated by histology, immunohistochemistry, and next-generation sequencing of the TP53 gene locus.
View Article and Find Full Text PDFBackground/aim: Metastatic prostate cancer (mPCa) results in high morbidity and mortality. Visceral metastases in particular are associated with a shortened survival. Our aim was to unravel the molecular mechanisms that underly pulmonary spread in mPCa.
View Article and Find Full Text PDFUrothelial bladder cancer (UC) has a wide tumor biological spectrum with challenging prognostic stratification and relevant therapy-associated morbidity. Most molecular classifications relate only indirectly to the therapeutically relevant protein level. We improve the pre-analytics of clinical samples for proteome analyses and characterize a cohort of 434 samples with 242 tumors and 192 paired normal mucosae covering the full range of UC.
View Article and Find Full Text PDFIntroduction: Pancreatic acinar cell carcinomas are rare malignant neoplasms. High-quality evidence about the best treatment strategy is lacking. We present the case of a 52-year-old male with a BRAF -mutated PACC who experienced a complete remission after chemotherapy with BRAF-/MEK-inhibitors.
View Article and Find Full Text PDFBackground/aim: Head and neck squamous cell carcinoma (HNSCC) represents a heterogeneous malignant disease of the oral cavity, pharynx, and larynx. HNSCC cells evade the host immune system through alterations in their immunogenicity, production of immunosuppressive mediators, and induction of immunomodulatory cell types. The immune status of solid HNSCC can be considered as hot, cold, or excluded for each patient individually, based on the distribution of tumor infiltrating immune cells.
View Article and Find Full Text PDFLung cancer is the leading cause of cancer-related deaths worldwide with lung adenocarcinoma (LUAD) being the most common type. Genomic studies of LUAD have advanced our understanding of its tumor biology and accelerated targeted therapy. However, the proteomic characteristics of LUAD are still insufficiently explored.
View Article and Find Full Text PDFBackground: Despite promising results of targeted therapy approaches, non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related death. Tripartite motif containing 11 (TRIM11) is part of the TRIM family of proteins, playing crucial roles in tumor progression. TRIM11 serves as an oncogene in various cancer types and has been reported to be associated with a poor prognosis.
View Article and Find Full Text PDFProstate cancer (PCa) remains the most commonly diagnosed cancer in men worldwide and is still the second leading cause of cancer-related death. One major cause of PCa development is epigenetic aberration, including histone modification. We have previously demonstrated that Lysine Demethylase 5C (KDM5C) plays an essential role in the development of PCa and drives PCa progression by promoting epithelial-mesenchymal transition.
View Article and Find Full Text PDFColorectal cancer is a notorious disease, with almost half of the patients succumbing to the disease. The prevalence and incidence rates of colorectal cancer are increasing in many parts of the world, highlighting the need to discover new biomarkers for diagnosis and therapy. Caldesmon (CaD), an actin-binding protein that plays a significant role in controlling cell motility, has emerged as a promising biomarker.
View Article and Find Full Text PDFAndrogen deprivation therapy has a central role in the treatment of advanced prostate cancer, often causing initial tumour remission before increasing independence from signal transduction mechanisms of the androgen receptor and then eventual disease progression. Novel treatment approaches are urgently needed, but only a fraction of promising drug candidates from the laboratory will eventually reach clinical approval, highlighting the demand for critical assessment of current preclinical models. Such models include standard, genetically modified and patient-derived cell lines, spheroid and organoid culture models, scaffold and hydrogel cultures, tissue slices, tumour xenograft models, patient-derived xenograft and circulating tumour cell eXplant models as well as transgenic and knockout mouse models.
View Article and Find Full Text PDFBone metastatic (BM) prostate cancer (PCa) belongs to the most lethal form of PCa, and therapeutic options are limited. Molecular profiling of metastases contributes to the understanding of mechanisms defining the bone metastatic niche. Our aim was to explore the transcriptional profile of PCa BM and to identify genes that drive progression.
View Article and Find Full Text PDFAim: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related death globally despite promising progress of personalized therapy approaches. Cyclin-dependent kinase 7 (CDK7) is a kinase involved in transcription, overexpressed in a broad spectrum of cancer types and found to be associated with an unfavourable prognosis. In this study, we aimed to investigate the protein expression of CDK7 in a large cohort of NSCLC incorporating adenocarcinomas (adNSCLC) and squamous cell carcinomas (sqNSCLC) and to correlate its expression with clinicopathological data.
View Article and Find Full Text PDFWorld J Gastrointest Oncol
September 2022
Colorectal cancer (CRC) is a devastating disease, mainly because of metastasis. As a result, there is a need to better understand the molecular basis of invasion and metastasis and to identify new biomarkers and therapeutic targets to aid in managing these tumors. The actin cytoskeleton and actin-binding proteins are known to play an important role in the process of cancer metastasis because they control and execute essential steps in cell motility and contractility as well as cell division.
View Article and Find Full Text PDFBackground: Head and neck squamous cell carcinomas (HNSCCs) are among the most common cancers in humans worldwide and have a rather poor prognosis. TRIM24 has various intracellular functions and was identified in other cancer entities as a poor prognostic factor for patients.
Methods: The expression of TRIM24 was evaluated by using immunohistochemistry.
Purpose: Nucleoporins as components of the nuclear pore complex (NCP) are known for regulating nuclear-cytoplasmatic transport. Recently, the nucleoporin POM121 was found to have an important impact on intranuclear translocation of prostate cancer (PCa)-specific tumor drivers including the androgen receptor (AR). The aim of our study was to assess the potential of POM121 as a prognostic biomarker.
View Article and Find Full Text PDFHead and neck squamous cell carcinomas (HNSCC) are among the most common cancers worldwide and are associated with a poor prognosis for patients. Among HNSCC, those originating in the hypopharynx have the worst prognosis. The histone demethylase LSD1 has been shown to promote cancer initiation, progression, and relapse through various mechanisms and is upregulated in many cancer tissues.
View Article and Find Full Text PDFCyclin-dependent kinase (CDK) 7-mediated phosphorylation of Mediator-complex subunit 1 (MED1) enhances androgen receptor (AR) activity in prostate cancer (PCa). Hyperactive AR-signalling plays a key role for the development of castration resistance. Several CDK7 inhibitors are currently under investigation in Phase I/II trials addressing solid tumours, including PCa.
View Article and Find Full Text PDFObjectives: Formalin-fixed paraffin-embedded (FFPE) tissue is the standard material for diagnostic pathology but poses relevant hurdles to accurate protein extraction due to cross-linking and chemical alterations. While numerous extraction protocols and chemicals have been described, systematic comparative analyses are limited. Various parameters were thus investigated in their qualitative and quantitative effects on protein extraction (PE) efficacy.
View Article and Find Full Text PDFProstate cancer (PCa) poses a major public health problem in men. Metastatic PCa is incurable, and ultimately threatens the life of many patients. Mutations in tumor suppressor genes and oncogenes are important for PCa progression, whereas the role of epigenetic factors in prostate carcinogenesis is insufficiently examined.
View Article and Find Full Text PDFProgression of prostate cancer (PCa) is characterized by metastasis and castration resistance after response to androgen deprivation. Therapeutic options are limited, causing high morbidity and lethality. Recent work reported pro-oncogenic implications of the Mediator subunits cyclin-dependent kinase (CDK) 8 and 19 for the progression of PCa.
View Article and Find Full Text PDFProstate cancer is a hormone-driven disease and its tumor cell growth highly relies on increased androgen receptor (AR) signaling. Therefore, targeted therapy directed against androgen synthesis or AR activation is broadly used and continually improved. However, a subset of patients eventually progresses to castration-resistant disease.
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