المؤلفون: Annalisa Comandatore, Marika Franczak, Ryszard T. Smolenski, Luca Morelli, Godefridus J. Peters, Elisa Giovannetti

المصدر: Comandatore, A, Franczak, M, Smolenski, R T, Morelli, L, Peters, G J & Giovannetti, E 2022, ' Lactate Dehydrogenase and its clinical significance in pancreatic and thoracic cancers ', Seminars in Cancer Biology, vol. 86, pp. 93-100 . https://doi.org/10.1016/j.semcancer.2022.09.001Test

مصطلحات موضوعية: Isoenzymes, Pancreatic Neoplasms, Mesothelioma, Cancer Research, Lung Neoplasms, L-Lactate Dehydrogenase, Pleural Neoplasms, Humans, Lactate Dehydrogenase 5, Thoracic Neoplasms, Energy Metabolism, Glycolysis

الوصف: The energy metabolism of tumor cells is considered one of the hallmarks of cancer because it is different from normal cells and mainly consists of aerobic glycolysis, fatty acid oxidation, and glutaminolysis. It is about one hundred years ago since Warburg observed that cancer cells prefer aerobic glycolysis even in normoxic conditions, favoring their high proliferation rate. A pivotal enzyme driving this phenomenon is lactate dehydrogenase (LDH), and this review describes prognostic and therapeutic opportunities associated with this enzyme, focussing on tumors with limited therapeutic strategies and life expectancy (i.e., pancreatic and thoracic cancers). Expression levels of LDH-A in pancreatic cancer tissues correlate with clinicopathological features: LDH-A is overexpressed during pancreatic carcinogenesis and showed significantly higher expression in more aggressive tumors. Similarly, LDH levels are a marker of negative prognosis in patients with both adenocarcinoma or squamous cell lung carcinoma, as well as in malignant pleural mesothelioma. Additionally, serum LDH levels may play a key role in the clinical management of these diseases because they are associated with tissue damage induced by tumor burden. Lastly, we discuss the promising results of strategies targeting LDH as a treatment strategy, reporting recent preclinical and translational studies supporting the use of LDH-inhibitors in combinations with current/novel chemotherapeutics that can synergistically target the oxygenated cells present in the tumor.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fbffd69adc411ad8662a2003aec46746Test
https://pubmed.ncbi.nlm.nih.gov/36096316Test

المؤلفون: Katarina D. Andini, Geert Kazemier, Godefridus J. Peters, Elisa Giovannetti, Lenka N.C. Boyd

المساهمون: Surgery, Medical oncology laboratory, CCA - Cancer biology and immunology, CCA - Imaging and biomarkers, Amsterdam Gastroenterology Endocrinology Metabolism

المصدر: Boyd, L N C, Andini, K D, Peters, G J, Kazemier, G & Giovannetti, E 2021, ' Heterogeneity and plasticity of cancer-associated fibroblasts in the pancreatic tumor microenvironment ', Seminars in Cancer Biology . https://doi.org/10.1016/j.semcancer.2021.03.006Test
Seminars in Cancer Biology. Academic Press Inc.

مصطلحات موضوعية: 0301 basic medicine, Cancer Research, Pancreatic ductal adenocarcinoma, endocrine system diseases, Carcinogenesis, Aggressive disease, medicine.disease_cause, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Cancer-Associated Fibroblasts, Pancreatic tumor, medicine, Tumor Microenvironment, Humans, Research evidence, Tumor microenvironment, business.industry, medicine.disease, digestive system diseases, Pancreatic Neoplasms, 030104 developmental biology, 030220 oncology & carcinogenesis, Cancer research, business, Carcinoma, Pancreatic Ductal

الوصف: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a notably poor prognosis, in urgent need of improved treatment strategies. The desmoplastic PDAC tumor microenvironment (TME), marked by a high concentration of cancer-associated-fibroblasts (CAFs), is a dynamic part of PDAC pathophysiology which occasions a variety of effects throughout the course of pancreatic tumorigenesis and disease evolution. A better understanding of the desmoplastic TME and CAF biology in particular, should provide new opportunities for improving therapeutics. That CAFs have a tumor-supportive role in oncogenesis is well known, yet research evidence has shown that CAFs also have tumor-repressive functions. In this review, we seek to clarify the intriguing heterogeneity and plasticity of CAFs and their ambivalent role in PDAC tumorigenesis and progression. Additionally, we provide recommendations to advance the implementation of CAF-directed PDAC care. An improved understanding of CAFs’ origins, spatial location, functional diversity, and marker determination, as well as CAF behavior during the course of PDAC progression and metastasis will provide essential knowledge for the future improvement of therapeutic strategies for patients suffering from PDAC.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3d5456c023986787b966ada372e77348Test
https://pubmed.ncbi.nlm.nih.gov/33737108Test

المؤلفون: Angela Listì, Christian D. Rolfo, Francesco Passiglia, Ignacio Gil-Bazo, Luis E. Raez, Antonio Russo, Paolo Manca, Joseph A. Pinto, Simona Taverna, Elisa Giovannetti, Christian Caglevic

المساهمون: Passiglia, F., Caglevic, C., Giovannetti, E., Pinto, JA., Manca, P., Taverna, S., Listì, A., Gil-Bazo, I., Raez, LE., Russo, A., Rolfo, C.

المصدر: Seminars in cancer biology
Passiglia, F, Caglevic, C, Giovannetti, E, Pinto, J A, Manca, P, Taverna, S, Listì, A, Gil-Bazo, I, Raez, L E, Russo, A & Rolfo, C 2018, ' Primary and metastatic brain cancer genomics and emerging biomarkers for immunomodulatory cancer treatment ', Seminars in Cancer Biology, vol. 52, no. Pt 2, pp. 259-268 . https://doi.org/10.1016/j.semcancer.2018.01.015Test

مصطلحات موضوعية: 0301 basic medicine, Cancer Research, Settore MED/06 - Oncologia Medica, medicine.medical_treatment, Biomarkers, Brain, CTLA4, Immunotherapy, Metastasis, PD1/PDL1, Genomics, Metastasi, Immunomodulation, 03 medical and health sciences, 0302 clinical medicine, medicine, Biomarkers, Tumor, Cytotoxic T cell, Animals, Humans, Primary (chemistry), business.industry, Brain Neoplasms, Immunogenicity, Biomarker, medicine.disease, Cancer treatment, 030104 developmental biology, 030220 oncology & carcinogenesis, Toxicity, Cancer research, Human medicine, business

الوصف: Recent studies with immunomodulatory agents targeting both cytotoxic T-lymphocyte protein 4 (CTLA4) and programmed cell death 1 (PD1)/programmed cell death ligand 1 (PDL1) have shown to be very effective in several cancers revealing an unexpected great activity in patients with both primary and metastatic brain tumors. Combining anti-CTLA4 and anti-PD1 agents as upfront systemic therapy has revealed to further increase the clinical benefit observed with single agent, even at cost of higher toxicity. Since the brain is an immunological specialized area it's crucial to establish the specific composition of the brain tumors' micro environment in order to predict the potential activity of immunomodulatory agents. This review briefly summarizes the basis of the brain immunogenicity, providing the most updated clinical evidences in terms of immune-checkpoint inhibitors efficacy and toxicity in both primary and metastatic brain tumors with the final aim of defining potential biomarkers for immunomodulatory cancer treatment.

وصف الملف: pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::40b71b1dfaf531ceed0915a34a319060Test
https://hdl.handle.net/10067/1547650151162165141Test

المؤلفون: H.W.M. van Laarhoven, Connie R. Jimenez, Elisa Giovannetti, Maarten F. Bijlsma, Geert Kazemier, T.Y.S. Le Large

المصدر: Le Large, T Y S, Bijlsma, M F, Kazemier, G, van Laarhoven, H W M, Giovannetti, E & Jimenez, C R 2017, ' Key biological processes driving metastatic spread of pancreatic cancer as identified by multi-omics studies ', Seminars in Cancer Biology, vol. 44, pp. 153-169 . https://doi.org/10.1016/j.semcancer.2017.03.008Test
Seminars in cancer biology (2017). doi:10.1016/j.semcancer.2017.03.008
info:cnr-pdr/source/autori:Le Large T.Y.S.; Bijlsma M.F.; Kazemier G.; van Laarhoven H.W.M.; Giovannetti E.; Jimenez C.R./titolo:Key biological processes driving metastatic spread of pancreatic cancer as identified by multi-omics studies/doi:10.1016%2Fj.semcancer.2017.03.008/rivista:Seminars in cancer biology/anno:2017/pagina_da:/pagina_a:/intervallo_pagine:/volume

مصطلحات موضوعية: 0301 basic medicine, Proteomics, Cancer Research, Biology, Adenocarcinoma, Malignancy, Bioinformatics, medicine.disease_cause, Metastasis, Pancreatic ductal adenocarcinoma, 03 medical and health sciences, 0302 clinical medicine, Pancreatic cancer, Genetics, medicine, Humans, Neoplasm Metastasis, Transcriptomics, Phosphoproteomics, medicine.disease, Prognosis, Primary tumor, digestive system diseases, Neoplasm Proteins, Gene Expression Regulation, Neoplastic, 030104 developmental biology, 030220 oncology & carcinogenesis, Cancer cell, Mutation, Cancer research, KRAS, Carcinoma, Pancreatic Ductal

الوصف: Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy, characterized by a high metastatic burden, already at the time of diagnosis. The metastatic potential of PDAC is one of the main reasons for the poor outcome next to lack of significant improvement in effective treatments in the last decade. Key mutated driver genes, such as activating KRAS mutations, are concordantly expressed in primary and metastatic tumors. However, the biology behind the metastatic potential of PDAC is not fully understood. Recently, large-scale omic approaches have revealed new mechanisms by which PDAC cells gain their metastatic potency. In particular, genomic studies have shown that multiple heterogeneous subclones reside in the primary tumor with different metastatic potential. The development of metastases may be correlated to a more mesenchymal transcriptomic subtype. However, for cancer cells to survive in a distant organ, metastatic sites need to be modulated into pre-metastatic niches. Proteomic studies identified the influence of exosomes on the Kuppfer cells in the liver, which could function to prepare this tissue for metastatic colonization. Phosphoproteomics adds an extra layer to the established omic techniques by unravelling key functional signaling. Future studies integrating results from these large-scale omic approaches will hopefully improve PDAC prognosis through identification of new therapeutic targets and patient selection tools. In this article, we will review the current knowledge on the biology of PDAC metastasis unravelled by large scale multi-omic approaches.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::39f946738e266020f164493ee81ce897Test