Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Precision Medicine Targeting FGFR2 Genomic Alterations in Advanced Cholangiocarcinoma: Current State and Future Perspectives.

ABSTRACT: Although a relatively uncommon tumor, cholangiocarcinoma is on the rise globally. Of note, most patients are diagnosed with metastatic disease, and the prognosis is poor with cytotoxic chemotherapy. Strategies targeting specific genomic alterations have demonstrated promising activity in recent years and could represent a new therapeutic avenue for these patients. In this review, we will address the biology and clinical results of FGFR inhibition in intrahepatic cholangiocarcinoma, highlighting limitations associated with treatment and discussing the use of circulating tumor DNA to detect mechanisms of resistance.

SUBMITTER: Zugman M

PROVIDER: S-EPMC9013963 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Precision Medicine Targeting <i>FGFR2</i> Genomic Alterations in Advanced Cholangiocarcinoma: Current State and Future Perspectives.

Zugman Miguel M Botrus Gehan G Pestana Roberto Carmagnani RC Uson Junior Pedro Luiz Serrano PLS

Frontiers in oncology 20220404

Although a relatively uncommon tumor, cholangiocarcinoma is on the rise globally. Of note, most patients are diagnosed with metastatic disease, and the prognosis is poor with cytotoxic chemotherapy. Strategies targeting specific genomic alterations have demonstrated promising activity in recent years and could represent a new therapeutic avenue for these patients. In this review, we will address the biology and clinical results of FGFR inhibition in intrahepatic cholangiocarcinoma, highlighting ...[more]

PMID: 35444941

Similar Datasets

Transcriptional profiling of microglia; current state of the art and future perspectives

Project description:Microglia are the tissue macrophages of the central nervous system (CNS) and the first to respond to CNS dysfunction and disease. Gene expression profiling of microglia during development, under homeostatic conditions and in the diseased CNS provided insight in microglia functions and changes thereof. Single cell sequencing studies further contributed to our understanding of microglia heterogeneity in relation to age, sex and CNS disease. Recently, single nucleus gene expression profiling was performed on (frozen) CNS tissue. Transcriptomic profiling of CNS tissues by (single) nucleus RNA-sequencing has the advantage that it can be applied to archived and well stratified frozen specimens. Here, we give an overview of the significant advances recently made in microglia transcriptional profiling. In addition, we present matched cellular and nuclear microglia RNA-seq datasets we generated from mouse and human CNS tissue to compare cellular versus nuclear transcriptomes from fresh and frozen samples. We demonstrate that microglia can be similarly profiled with cell and nucleus profiling, and importantly also with nuclei isolated from frozen tissue. Nuclear microglia transcriptomes are a reliable proxy for cellular transcriptomes. Interestingly, lipopolysaccharide- (LPS)-induced changes in gene expression were even more pronounced in the nuclear transcriptome. In addition, heterogeneity in microglia observed in fresh samples is similarly detected in frozen nuclei of the same donor. Together, these results show that microglia nuclear RNAs obtained from frozen CNS tissue are a reliable proxy for microglia gene expression and cellular heterogeneity and may prove an effective strategy to study of the role of microglia in neuropathology.

2019-08-10 | GSE135618 | GEO

Current Strategies and Future Perspectives for Precision Medicine in Pancreatic Cancer.

Project description:Current standard-of-care for patients with pancreatic ductal adenocarcinoma (PDAC) focusses on chemotherapeutic regimens and pancreatic cancer surgery. However, limited treatment options, late diagnosis in advanced tumor stages and the aggressive behavior of PDAC contribute to the high mortality of the disease. Consequently, there is an urgent need of precision medicine for pancreatic cancer patients. All over the world, numerous initiatives started in recent years to translate novel scientific discoveries into prospective clinical trials. One major approach pursues the stratification of PDAC patients according the tumor transcriptome to predict treatment response. Other strategies concentrate on genomic alterations and the identification of individualized targeted therapies. Further experimental studies are ongoing to detect novel biomarkers for cancer diagnosis, subtyping, treatment response prediction or clinical outcome. However, the challenge remains to transfer the knowledge into clinical practice. In this review, we summarize current literature and knowledge and highlight novel concepts of basic and clinical research uncovering suitable biomarkers and targeted therapies. Thus, we provide an overview of preclinical and clinical efforts of precision medicine in pancreatic cancer.

| S-EPMC7226595 | biostudies-literature

Precision Medicine in Cholangiocarcinoma: Past, Present, and Future.

Project description:Cholangiocarcinoma (CCA), or biliary tract cancer, has a poor prognosis. The median survival time among patients with CCA is under 2 years from diagnosis, and the global 5-year survival rate is only 10%. First-line therapy with chemotherapeutic agents, gemcitabine plus cisplatin, has traditionally been used to treat unresectable advanced CCA. In recent years, precision medicine has become a mainstream cancer treatment due to innovative next-generation sequencing technology. Several genetic alterations, including mutations, gene fusions, and copy number variations, have been found in CCA. In this review, we summarized the current understanding of genetic profiling in CCA and targeted therapy in CCA. Owing to the high heterogeneity of CCA, tumor microenvironmental factors, and the complexity of tumor biology, only pemigatinib, infigratinib, ivosidenib, larotrbctinib, and entrectinib are currently approved for the treatment of CCA patients with fibroblast growth factor receptor 2 gene (FGFR2) fusion, isocitrate dehydrogenase gene (IDH1) mutation, and neurotrophin receptor tyrosine kinase gene (NRTK) fusion, respectively. Additional targeted therapies, including other FGFR2 inhibitors, PI3K/AKT/mTOR inhibitors, and BRAF-directed targeted therapy, have been discussed for the management of CCA, and immune checkpoint inhibitors, particularly pembrolizumab, can be administered to patients with high microsatellite instability tumors. There is a further need for improvement in precision medicine therapies in the treatment of CCA and discuss the approved and potential targeted therapies for CCA.

| S-EPMC9225212 | biostudies-literature

Molecular and Phenotypic Profiling for Precision Medicine in Pancreatic Cancer: Current Advances and Future Perspectives.

Project description:Pancreatic cancer is the most common lethal malignancy, with little improvement in patient outcomes over the decades. The development of early detection methods and effective therapeutic strategies are needed to improve the prognosis of patients with this disease. Recent advances in cancer genomics have revealed the genetic landscape of pancreatic cancer, and clinical trials are currently being conducted to match the treatment to underlying mutations. Liquid biopsy-based diagnosis is a promising method to start personalized treatment. In addition to genome-based medicine, personalized models have been studied as a tool to test candidate drugs to select the most efficacious treatment. The innovative three-dimensional organoid culture platform, as well as patient-derived xenografts can be used to conduct genomic and functional studies to enable personalized treatment approaches. Combining genome-based medicine with drug screening based on personalized models may fulfill the promise of precision medicine for pancreatic cancer.

| S-EPMC8260689 | biostudies-literature

Recurrent Glioblastoma Treatment: State of the Art and Future Perspectives in the Precision Medicine Era.

Project description:Current treatment guidelines for the management of recurrent glioblastoma (rGBM) are far from definitive, and the prognosis remains dismal. Despite recent advancements in the pharmacological and surgical fields, numerous doubts persist concerning the optimal strategy that clinicians should adopt for patients who fail the first lines of treatment and present signs of progressive disease. With most recurrences being located within the margins of the previously resected lesion, a comprehensive molecular and genetic profiling of rGBM revealed substantial differences compared with newly diagnosed disease. In the present comprehensive review, we sought to examine the current treatment guidelines and the new perspectives that polarize the field of neuro-oncology, strictly focusing on progressive disease. For this purpose, updated PRISMA guidelines were followed to search for pivotal studies and clinical trials published in the last five years. A total of 125 articles discussing locoregional management, radiotherapy, chemotherapy, and immunotherapy strategies were included in our analysis, and salient findings were critically summarized. In addition, an in-depth description of the molecular profile of rGBM and its distinctive characteristics is provided. Finally, we integrate the above-mentioned evidence with the current guidelines published by international societies, including AANS/CNS, EANO, AIOM, and NCCN.

| S-EPMC9405902 | biostudies-literature

IDH1 Targeting as a New Potential Option for Intrahepatic Cholangiocarcinoma Treatment-Current State and Future Perspectives.

Project description:Cholangiocarcinoma is a primary malignancy of the biliary tract characterized by late and unspecific symptoms, unfavorable prognosis, and few treatment options. The advent of next-generation sequencing has revealed potential targetable or actionable molecular alterations in biliary tumors. Among several identified genetic alterations, the IDH1 mutation is arousing interest due to its role in epigenetic and metabolic remodeling. Indeed, some IDH1 point mutations induce widespread epigenetic alterations by means of a gain-of-function of the enzyme, which becomes able to produce the oncometabolite 2-hydroxyglutarate, with inhibitory activity on α-ketoglutarate-dependent enzymes, such as DNA and histone demethylases. Thus, its accumulation produces changes in the expression of several key genes involved in cell differentiation and survival. At present, small-molecule inhibitors of IDH1 mutated enzyme are under investigation in preclinical and clinical phases as promising innovative treatments for IDH1-mutated intrahepatic cholangiocarcinomas. This review examines the molecular rationale and the results of preclinical and early-phase studies on novel pharmacological agents targeting mutant IDH1 in cholangiocarcinoma patients. Contextually, it will offer a starting point for discussion on combined therapies with metabolic and epigenetic drugs, to provide molecular support to target the interplay between metabolism and epigenetics, two hallmarks of cancer onset and progression.

| S-EPMC7464324 | biostudies-literature

Immunotherapy for Biliary Tract Cancer in the Era of Precision Medicine: Current Knowledge and Future Perspectives.

Project description:Biliary tract cancers (BTC) represent a heterogeneous and aggressive group of tumors with dismal prognosis. For a long time, BTC has been considered an orphan disease with very limited therapeutic options. In recent years a better understanding of the complex molecular landscape of biology is rapidly changing the therapeutic armamentarium. However, while 40-50% of patients there are molecular drivers susceptible to target therapy, for the remaining population new therapeutic options represent an unsatisfied clinical need. The role of immunotherapy in the continuum of treatment of patients with BTC is still debated. Despite initial signs of antitumor-activity, single-agent immune checkpoint inhibitors (ICIs) demonstrated limited efficacy in an unselected population. Therefore, identifying the best partner to combine ICIs and predictive biomarkers represents a key challenge to optimize the efficacy of immunotherapy. This review provides a critical analysis of completed trials, with an eye on future perspectives and possible biomarkers of response.

| S-EPMC8775359 | biostudies-literature

Predictive Biomarkers of Response to Neoadjuvant Chemotherapy in Breast Cancer: Current and Future Perspectives for Precision Medicine.

Project description:Pathological complete response (pCR) after neoadjuvant chemotherapy in patients with early breast cancer is correlated with better survival. Meanwhile, an expanding arsenal of post-neoadjuvant treatment strategies have proven beneficial in the absence of pCR, leading to an increased use of neoadjuvant systemic therapy in patients with early breast cancer and the search for predictive biomarkers of response. The better prediction of response to neoadjuvant chemotherapy could enable the escalation or de-escalation of neoadjuvant treatment strategies, with the ultimate goal of improving the clinical management of early breast cancer. Clinico-pathological prognostic factors are currently used to estimate the potential benefit of neoadjuvant systemic treatment but are not accurate enough to allow for personalized response prediction. Other factors have recently been proposed but are not yet implementable in daily clinical practice or remain of limited utility due to the intertumoral heterogeneity of breast cancer. In this review, we describe the current knowledge about predictive factors for response to neoadjuvant chemotherapy in breast cancer patients and highlight the future perspectives that could lead to the better prediction of response, focusing on the current biomarkers used for clinical decision making and the different gene signatures that have recently been proposed for patient stratification and the prediction of response to therapies. We also discuss the intratumoral phenotypic heterogeneity in breast cancers as well as the emerging techniques and relevant pre-clinical models that could integrate this biological factor currently limiting the reliable prediction of response to neoadjuvant systemic therapy.

| S-EPMC9405974 | biostudies-literature

Precision medicine in cholangiocarcinoma.

Project description:Cholangiocarcinoma is one of the epithelial cancers with the poorest prognosis and the narrowest therapeutic choice in humans. Compared with other cancer types, cholangiocarcinoma has been often neglected by oncology and liver research studies, thereby leaving many issues unsolved. Apart from the early and marked aggressiveness, one of the main reasons of the still unsatisfying clinical management of cholangiocarcinoma is its wide tumor heterogeneity needing more than other diseases a 'precision medicine' approach. In this regard, in the last few years there has been an awakening of interest aimed at dissecting the complex molecular and genomic profile of cholangiocarcinoma. Thus, a range of molecular players have been recently identified as putative mechanistic determinants of cholangiocarcinoma invasiveness, encompassing tyrosine kinase receptors, metabolic enzymes, transcription factors, small GTPases, ubiquitin ligases, and chromatin-remodelling proteins, whose aberrant expression may derive from stochastic mutations as well as from pro-oncogenic paracrine signals released by the stromal microenvironment, which is particularly exuberant in cholangiocarcinoma. Herein, we sought to overview the most relevant observations unravelling the genomic landscape of cholangiocarcinoma, and the prognostic and predictive biomarkers that consequently have been emerging. Then, we will discuss innovative treatment approaches derived from conventional chemotherapy, targeted therapies, antiangiogenic therapies and immunotherapy, and how they are opening new avenues towards a precision medicine in cholangiocarcinoma.

| S-EPMC6087799 | biostudies-literature

CRISPR/Cas9 Landscape: Current State and Future Perspectives.

Project description:CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 is a unique genome editing tool that can be easily used in a wide range of applications, including functional genomics, transcriptomics, epigenetics, biotechnology, plant engineering, livestock breeding, gene therapy, diagnostics, and so on. This review is focused on the current CRISPR/Cas9 landscape, e.g., on Cas9 variants with improved properties, on Cas9-derived and fusion proteins, on Cas9 delivery methods, on pre-existing immunity against CRISPR/Cas9 proteins, anti-CRISPR proteins, and their possible roles in CRISPR/Cas9 function improvement. Moreover, this review presents a detailed outline of CRISPR/Cas9-based diagnostics and therapeutic approaches. Finally, the review addresses the future expansion of genome editors' toolbox with Cas9 orthologs and other CRISPR/Cas proteins.

| S-EPMC10671331 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data