Recent advances in understanding the complexities of metastasis.
Ontology highlight
ABSTRACT:
SUBMITTER: Chitty JL
PROVIDER: S-EPMC6073095 | biostudies-literature | 2018
REPOSITORIES: biostudies-literature
Publications
Recent advances in understanding the complexities of metastasis.
Chitty Jessica L JL Filipe Elysse C EC Lucas Morghan C MC Herrmann David D Cox Thomas R TR Timpson Paul P
F1000Research 20180801
Tumour metastasis is a dynamic and systemic process. It is no longer seen as a tumour cell-autonomous program but as a multifaceted and complex series of events, which is influenced by the intrinsic cellular mutational burden of cancer cells and the numerous bidirectional interactions between malignant and non-malignant cells and fine-tuned by the various extrinsic cues of the extracellular matrix. In cancer biology, metastasis as a process is one of the most technically challenging aspects of c ...[more]
Similar Datasets
Project description:Vitiligo, an acquired depigmentation disorder, manifests as white macules on the skin and can cause significant psychological stress and stigmatization. Recent advances have shed light on key components that drive disease onset and progression as well as therapeutic approaches. Vitiligo can be triggered by stress to the melanin pigment-producing cells of the skin, the melanocytes. The triggers, which range from sunburn to mechanical trauma and chemical exposures, ultimately cause an autoimmune response that targets melanocytes, driving progressive skin depigmentation. The most significant progress in our understanding of disease etiology has been made on three fronts: (1) identifying cellular responses to stress, including antioxidant pathways and the unfolded protein response (UPR), as key players in disease onset, (2) characterizing immune responses that target melanocytes and drive disease progression, and (3) identifying major susceptibility genes. The current model for vitiligo pathogenesis postulates that oxidative stress causes cellular disruptions, including interruption of protein maturation in the endoplasmic reticulum (ER), leading to the activation of the UPR and expression of UPR-regulated chemokines such as interleukin 6 (IL-6) and IL-8. These chemokines recruit immune components to the skin, causing melanocytes to be targeted for destruction. Oxidative stress can further increase melanocyte targeting by promoting antigen presentation. Two key components of the autoimmune response that promote disease progression are the interferon (IFN)-?/CXCL10 axis and IL-17-mediated responses. Several genome-wide association studies support a role for these pathways, with the antioxidant gene NRF2, UPR gene XBP1, and numerous immune-related genes including class I and class II major histocompatibility genes associated with a risk for developing vitiligo. Novel approaches to promote repigmentation in vitiligo are being investigated and may yield effective, long-lasting therapies.
| S-EPMC5017284 | biostudies-other
Project description:The definition of cholangiocarcinoma (CCA) encompasses all tumors originating in the epithelium of the bile ducts, including the intrahepatic bile ducts (ICCA) and extrahepatic bile ducts (ECCA). The incidence of ICCA and ECCA has increased in the last few decades, and molecular advances in both entities have brought understanding of their differences and allowed treatment advances aimed at personalized therapy. In this review, we discuss recent progress in the molecular landscape of CCAs, emerging treatment biomarker-guided strategies, and future insights into the management of advanced disease.
| S-EPMC7886064 | biostudies-literature
Project description:Exonic circular RNAs (circRNAs) have been discovered in all kingdoms of life. In many cases, the details of circRNA function and their involvement in cellular processes and diseases are not yet fully understood. However, the past few years have seen significant developments in bioinformatics and in experimental protocols that advance the ongoing research in this still-emerging field. Sophisticated methods for circRNA generation in vitro and in vivo have been developed, allowing model studies into circRNA function and application. We here review the ongoing circRNA research, giving special attention to recent progress in the field.
| S-EPMC7324948 | biostudies-literature
Project description:By definition, congenital myopathy typically presents with skeletal muscle weakness and hypotonia at birth. Traditionally, congenital myopathy subtypes have been predominantly distinguished on the basis of the pathological hallmarks present on skeletal muscle biopsies. Many genes cause congenital myopathies when mutated, and a burst of new causative genes have been identified because of advances in gene sequencing technology. Recent discoveries include extending the disease phenotypes associated with previously identified genes and determining that genes formerly known to cause only dominant disease can also cause recessive disease. The more recently identified congenital myopathy genes account for only a small proportion of patients. Thus, the congenital myopathy genes remaining to be discovered are predicted to be extremely rare causes of disease, which greatly hampers their identification. Significant progress in the provision of molecular diagnoses brings important information and value to patients and their families, such as possible disease prognosis, better disease management, and informed reproductive choice, including carrier screening of parents. Additionally, from accurate genetic knowledge, rational treatment options can be hypothesised and subsequently evaluated in vitro and in animal models. A wide range of potential congenital myopathy therapies have been investigated on the basis of improved understanding of disease pathomechanisms, and some therapies are in clinical trials. Although large hurdles remain, promise exists for translating treatment benefits from preclinical models to patients with congenital myopathy, including harnessing proven successes for other genetic diseases.
| S-EPMC6290972 | biostudies-literature
Project description:Frontotemporal degeneration (FTD) is a heterogeneous spectrum of neurodegenerative disorders characterized by diverse clinical presentations, neuropathological characteristics, and underlying genetic causes. In the last few years, several advances in the knowledge of clinical and biological aspects have been accomplished and three major scenarios have emerged that will represent the core issues in the FTD scene over the next few years. Foremost, the development of cerebrospinal fluid and blood biomarkers as well as neuroimaging techniques will aid the pursuit of new diagnostic and prognostic markers able to identify the ongoing proteinopathy and predict disease progression, which is key in identifying and stratifying patients for enrolment in clinical trials as well as evaluating response to treatment. On the other hand, current research has focused on the first attempts to slow down or revert disease progression, with the identification of disease modulators associated with disease onset and the ongoing development of the first pharmacological treatments for both sporadic and genetic FTD. Future research will certainly improve our knowledge of FTD and possibly open up a new era of disease-modifying therapies for this still-orphan disorder.
| S-EPMC6913220 | biostudies-literature
Project description:Antiphospholipid syndrome (APS), also known as Hughes Syndrome, is a systemic autoimmune disease characterized by thrombosis and/or pregnancy morbidity in the presence of persistently positive antiphospholipid antibodies. A patient with APS must meet at least one of two clinical criteria (vascular thrombosis or complications of pregnancy) and at least one of two laboratory criteria including the persistent presence of lupus anticoagulant (LA), anticardiolipin antibodies (aCL), and/or anti-b2 glycoprotein I (anti-b2GPI) antibodies of IgG or IgM isotype at medium to high titres in patient's plasma. However, several other autoantibodies targeting other coagulation cascade proteins (i.e. prothrombin) or their complex with phospholipids (i.e. phosphatidylserine/prothrombin complex), or to some domains of ?2GPI, have been proposed to be also relevant to APS. In fact, the value of testing for new aPL specificities in the identification of APS in thrombosis and/or pregnancy morbidity patients is currently being investigated.
| S-EPMC5224683 | biostudies-literature
Project description:There have been major recent advancements in the understanding and management of multiple myeloma. Diagnostic criteria have been revised and former ultra-high-risk smoldering multiple myeloma is now considered multiple myeloma in need of treatment. Understanding clonal progression, evolution, and tides not only has helped elucidate the disease behavior but might help expand therapeutic choices in order to select appropriate treatment for patients. Unprecedented response rates with modern triplet induction therapies containing proteasome inhibitor and immunomodulators have made this approach standard for initial treatment. The US Food and Drug Administration approved four new drugs (two targeted antibodies and two oral agents) in 2015 in relapsed/refractory multiple myeloma and these drugs along with the other already-available drugs have now increased the choices of regimens. Even drugs without single-agent activity, such as panobinostat and elotuzumab, have an important role, especially in the proteasome inhibitor refractory setting. Recent studies done in the context of novel agent induction suggest that high-dose therapy followed by autologous transplant continues to improve response rates and progression-free survival, thus underscoring their role in transplant-eligible patients. Evolving paradigms in the treatment of multiple myeloma include newer promising immune approaches, such as adoptive cellular therapies, vaccines, or antibody-based immune manipulations. Though multiple myeloma is still considered incurable, it is clear that with the improved understanding of disease biology and clonal architecture of relapse combined with the availability of multi-targeted approaches, we are ever closer to a lasting cure or transformation into indolent and long-lasting disease courses or both.
| S-EPMC4995679 | biostudies-literature
Project description:Gonadotropins are glycoprotein sex hormones regulating development and reproduction and bind to specific G protein-coupled receptors expressed in the gonads. Their effects on multiple signaling cascades and intracellular events have recently been characterized using novel technological and scientific tools. The impact of allosteric modulators on gonadotropin signaling, the role of sugars linked to the hormone backbone, the detection of endosomal compartments supporting signaling modules, and the dissection of different effects mediated by these molecules are areas that have advanced significantly in the last decade. The classic view providing the exclusive activation of the cAMP/protein kinase A (PKA) and the steroidogenic pathway by these hormones has been expanded with the addition of novel signaling cascades as determined by high-resolution imaging techniques. These new findings provided new potential therapeutic applications. Despite these improvements, unanswered issues of gonadotropin physiology, such as the intrinsic pro-apoptotic potential to these hormones, the existence of receptors assembled as heteromers, and their expression in extragonadal tissues, remain to be studied. Elucidating these issues is a challenge for future research.
| S-EPMC8130412 | biostudies-literature
Project description:Pancreatic ductal adenocarcinoma (PDAC) is an intractable cancer and a leading cause of cancer deaths worldwide. Over 90% of patients die within 1 year of diagnosis. Deaths from PDAC are increasing and it remains a cancer of substantial unmet need. A number of factors contribute to its poor prognosis: namely, late presentation, early metastases and limited systemic therapy options because of chemoresistance. A variety of research approaches underway are aimed at improving patient survival. Here, we review high-risk groups and efforts for early detection. We examine recent developments in the understanding of complex molecular and metabolic alterations which accompany PDAC. We explore artificial intelligence and biological targets for therapy and examine the role of tumour stroma and the immune microenvironment. We also review recent developments with respect to the PDAC microbiome. It is hoped that current research efforts will translate into earlier diagnosis, improvements in treatment and better outcomes for patients.
| S-EPMC9022729 | biostudies-literature
Project description:The achievements in the treatment of metastatic colorectal cancer during recent years are based on a better understanding of the disease and individualized regimen planning. In adjuvant treatment, the highly important IDEA (International Duration Evaluation of Adjuvant Chemotherapy) study has shown that treatment duration can safely be reduced in selected patient populations. In patients with pN1 and pT1-pT3 tumors, 3 months of treatment with 5-fluorouracil and oxaliplatin is comparable with respect to 3-year survival rate to 6 months of treatment. For patients with N2 tumors, 6 months of treatment should stay the standard of care. The limitation of the duration of the adjuvant treatment is significantly reducing the chemotherapy-induced morbidity. New studies will explore the use of immune-checkpoint inhibitors in the adjuvant setting in microsatellite-instable (MSI) tumors. In metastatic disease, next to the required molecular testing for RAS and BRAF mutations, MSI testing is recommended. In the rare group of patients with a MSI tumor, immune-checkpoint inhibition is changing the course of the disease dramatically. Therefore, it is important to identify those patients early. For the RAS-mutant cases, no new and targeted treatment options have been identified yet. An optimal treatment strategy for those patients is urgently needed. RAS wild-type patients with tumors derived from the left side of the colon (splenic flexure to rectum) should be treated in first line with epithelial growth factor receptor (EGFR) antibodies. This selection by a molecular and a clinical marker increased the benefit derived by EGFR antibodies dramatically and defined the most effective treatment option for those patients. New selection criteria based on gene expression, methylation, and other molecular changes are explored and will further influence our therapeutic strategies in the future.
| S-EPMC6173127 | biostudies-literature