Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cancer therapy in the necroptosis era.

ABSTRACT: Necroptosis is a caspase-independent form of regulated cell death executed by the receptor-interacting protein kinase 1 (RIP1), RIP3, and mixed lineage kinase domain-like protein (MLKL). Recently, necroptosis-based cancer therapy has been proposed to be a novel strategy for antitumor treatment. However, a big controversy exists on whether this type of therapy is feasible or just a conceptual model. Proponents believe that because necroptosis and apoptosis use distinct molecular pathways, triggering necroptosis could be an alternative way to eradicate apoptosis-resistant cancer cells. This hypothesis has been preliminarily validated by recent studies. However, some skeptics doubt this strategy because of the intrinsic or acquired defects of necroptotic machinery observed in many cancer cells. Moreover, two other concerns are whether or not necroptosis inducers are selective in killing cancer cells without disturbing the normal cells and whether it will lead to inflammatory diseases. In this review, we summarize current studies surrounding this controversy on necroptosis-based antitumor research and discuss the advantages, potential issues, and countermeasures of this novel therapy.

SUBMITTER: Su Z

PROVIDER: S-EPMC4832112 | biostudies-other | 2016 May

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

Cancer therapy and treatments during COVID-19 era.

Project description:The COVID-19 pandemic has put a serious strain on health treatments as well at the economies of many nations. Unfortunately, there is not currently available vaccine for SARS-Cov-2/COVID-19. Various types of patients have delayed treatment or even routine check-ups and we are adapting to a virtual world. In many cases, surgeries are delayed unless they are essential. This is also true with regards to cancer treatments and screening. Interestingly, some existing drugs and nutraceuticals have been screened for their effects on COVID-19. Certain FDA approved drugs, vitamin, natural products and trace minerals may be repurposed to treat or improve the prevention of COVID-19 infections and disease progression. This review article will summarize how the treatments of various cancer patients has changed during the COVID-19 era as well as discuss the promise of some existing drugs and other agents to be repurposed to treat this disease.

| S-EPMC7319627 | biostudies-literature

Necroptosis in tumorigenesis, activation of anti-tumor immunity, and cancer therapy.

Project description:While the mechanisms underlying apoptosis and autophagy have been well characterized over recent decades, another regulated cell death event, necroptosis, remains poorly understood. Elucidating the signaling networks involved in the regulation of necroptosis may allow this form of regulated cell death to be exploited for diagnosis and treatment of cancer, and will contribute to the understanding of the complex tumor microenvironment. In this review, we have summarized the mechanisms and regulation of necroptosis, the converging and diverging features of necroptosis in tumorigenesis, activation of anti-tumor immunity, and cancer therapy, as well as attempts to exploit this newly gained knowledge to provide therapeutics for cancer.

| S-EPMC5302997 | biostudies-literature

ABIN-1 is a key regulator in RIPK1-dependent apoptosis (RDA) and necroptosis, and ABIN-1 deficiency potentiates necroptosis-based cancer therapy in colorectal cancer.

Project description:ABIN-1, also called TNIP1, is an ubiquitin-binding protein that serves an important role in suppressing RIPK1-independent apoptosis, necroptosis, and NF-κB activation. However, the involvement of ABIN-1 in the regulation of RIPK1-dependent apoptosis (RDA) is unknown. In this study, we found that poly(I:C) + TAK1 inhibitor 5Z-7-oxozeaenol (P5) concurrently induces RDA and necroptosis in Abin-1-/-, but not in Abin-1+/+ mouse embryonic fibroblasts (MEFs). Upon P5 stimulation, cells initially die by necroptosis and subsequently by RDA. Furthermore, we explored the therapeutic effect of ABIN-1 deficiency in necroptosis-based cancer therapy in colorectal cancer (CRC). We found that poly(I:C) + 5Z-7-oxozeaenol + IDN-6556 (P5I) yields a robust pro-necroptosis response, and ABIN-1 deficiency additionally enhances this P5I-induced necroptosis. Moreover, phase I/II cIAP inhibitor birinapant with clinical caspase inhibitor IDN-6556 (BI) alone and 5-fluorouracil with IDN-6556 (FI) alone are sufficient to induce necroptotic cell death in CRC cells by promoting auto-secretion of tumor necrosis factor (TNF); ABIN-1 deficiency amplifies the BI- or FI-induced necroptosis. Two independent xenograft experiments using HT-29 or COLO205 cells show that both BI and P5I remarkably inhibit tumor growth via necroptosis activation. For poly(I:C)-induced cell death, the sensitizing effect of ABIN-1 deficiency on cell death may be attributed to increased expression of TLR3. In TNF-induced necroptosis, ABIN-1 deficiency increases TNF-induced RIPK1 polyubiquitination by reducing the recruitment of ubiquitin-editing enzyme A20 to the TNFR1 signaling complex and induces more TNF secretion in CRC cells upon pro-necroptosis stimulation. With this combined data, ABIN-1 deficiency promotes greater sensitization of CRC cells to necroptosis.

| S-EPMC7862295 | biostudies-literature

Adjuvant therapy for pancreas cancer in an era of value based cancer care.

Project description:In resected pancreas cancer, adjuvant therapy improves outcomes and is considered the standard of care for patients who recover sufficiently post operatively. Chemotherapy or combined chemotherapy and radiation therapy (chemoradiation; CRT) are strategies used in the adjuvant setting. However, there is a lack of evidence to suggest whether the addition of RT to chemotherapy translates to an improvement in clinical outcomes. This is true even when accounting for the subset of patients with a higher risk for recurrence, such as those with R1 and lymph node positive disease. When considering the direct and indirect costs, impact on quality of life and questionable added clinical benefit, the true "net health benefit" from added RT to chemotherapy becomes more uncertain. Future directions, including the utilization of modern RT, integration of novel therapies, and intensifying chemotherapy regimens may improve outcomes in resected pancreas cancer.

| S-EPMC4976619 | biostudies-literature

Proton beam therapy for cancer in the era of precision medicine.

Project description:Precision radiotherapy, which accurately delivers the dose on a tumor and confers little or no irradiation to the surrounding normal tissue and organs, results in maximum tumor control and decreases the toxicity to the utmost extent. Proton beam therapy (PBT) provides superior dose distributions and has a dosimetric advantage over photon beam therapy. Initially, the clinical practice and study of proton beam therapy focused on ocular tumor, skull base, paraspinal tumors (chondrosarcoma and chordoma), and unresectable sarcomas, which responded poorly when treated with photon radiotherapy. Then, it is widely regarded as an ideal mode for reirradiation and pediatrics due to reducing unwanted side effects by lessening the dose to normal tissue. During the past decade, the application of PBT has been rapidly increasing worldwide and gradually expanding for the treatment of various malignancies. However, to date, the role of PBT in clinical settings is still controversial, and there are considerable challenges in its application. We systematically review the latest advances of PBT and the challenges for patient treatment in the era of precision medicine.

| S-EPMC6290507 | biostudies-literature

Oncolytic virus therapy: A new era of cancer treatment at dawn.

Project description:Oncolytic virus therapy is perhaps the next major breakthrough in cancer treatment following the success in immunotherapy using immune checkpoint inhibitors. Oncolytic viruses are defined as genetically engineered or naturally occurring viruses that selectively replicate in and kill cancer cells without harming the normal tissues. T-Vec (talimogene laherparepvec), a second-generation oncolytic herpes simplex virus type 1 (HSV-1) armed with GM-CSF, was recently approved as the first oncolytic virus drug in the USA and Europe. The phase III trial proved that local intralesional injections with T-Vec in advanced malignant melanoma patients can not only suppress the growth of injected tumors but also act systemically and prolong overall survival. Other oncolytic viruses that are closing in on drug approval in North America and Europe include vaccinia virus JX-594 (pexastimogene devacirepvec) for hepatocellular carcinoma, GM-CSF-expressing adenovirus CG0070 for bladder cancer, and Reolysin (pelareorep), a wild-type variant of reovirus, for head and neck cancer. In Japan, a phase II clinical trial of G47?, a third-generation oncolytic HSV-1, is ongoing in glioblastoma patients. G47? was recently designated as a "Sakigake" breakthrough therapy drug in Japan. This new system by the Japanese government should provide G47? with priority reviews and a fast-track drug approval by the regulatory authorities. Whereas numerous oncolytic viruses have been subjected to clinical trials, the common feature that is expected to play a major role in prolonging the survival of cancer patients is an induction of specific antitumor immunity in the course of tumor-specific viral replication. It appears that it will not be long before oncolytic virus therapy becomes a standard therapeutic option for all cancer patients.

| S-EPMC5084676 | biostudies-literature

Circulating tumor DNA (ctDNA) in the era of personalized cancer therapy.

Project description:The heterogeneity of tumor is considered as a major difficulty to victorious personalized cancer medicine. There is an extremeneed of consistent response evaluation for in vivo tumor heterogeneity anditscoupledconflict mechanisms. In this occasion researchers will be able to keep pace withpredictive, preventive, personalized, and Participatory (P4) medicine for cancer managements. In fact tumor heterogeneity is a central part of cancer evolution,soin order to progress in understanding of the dynamics within a tumor some diagnostic apparatus should be improved. Latest molecular techniques like Next generation Sequencing (NGS) and ultra-deep sequencing could disclose some clones within a liquid tumor biopsy which mainly responsible of treatment resistance. Circulating tumor DNA (ctDNA) as a main component of liquid biopsy is agifted biomarker for cancer mutation tracking as well as profiling. Personalized medicine facilitate learning regarding to genetic pools of tumor and their possible respond to treatment which could be much easier by using of ctDNA.With this information, cliniciansarelooking forward to find the best strategies for prevention, screening, and treatment in the way of precision medicine. Currently, numerous clinical efficacy of such informative improved treatment are in hand. Here we represent the review of plasma-derived ctDNA studies use in personalized cancer managements.

| S-EPMC6154523 | biostudies-literature

Antibody-Drug Conjugates: Ushering in a New Era of Cancer Therapy.

Project description:Antibody-drug conjugates (ADCs) have provided new therapeutic options and significant promise for patients with cancer, particularly where existing treatments are limited. Substantial effort in ADC development is underway globally, with 13 ADCs currently approved and many more in development. The therapeutic benefits of ADCs leverage the ability to selectively target cancer cells through antibody binding, resultant relative sparing of non-malignant tissues, and the targeted delivery of a cytotoxic payload. Consequently, this drug class has demonstrated activity in multiple malignancies refractory to standard therapeutic options. Despite this, limitations exist, including narrow therapeutic windows, unique toxicity profiles, development of therapeutic resistance, and appropriate biomarker selection. This review will describe the development of ADCs, their mechanisms of action, pivotal trials, and approved indications and identify common themes. Current challenges and opportunities will be discussed for this drug class in cancer therapeutics at a time when significant developments in antibody therapies, immunotherapy, and targeted agents are occurring.

| S-EPMC10458257 | biostudies-literature

Exploiting Necroptosis for Therapy of Acute Lymphoblastic Leukemia.

Project description:Escape from chemotherapy-induced apoptosis is a hallmark of drug resistance in cancer. The recent identification of alternative programmed cell death pathways opens up for possibilities to circumvent the apoptotic blockade in drug resistant cancer and eliminate malignant cells. Indeed, we have recently shown that programmed necrosis, termed necroptosis, could be triggered to induce cell death in a subgroup of primary acute lymphoblastic leukemia (ALL) including highly refractory relapsed cases. In this review we focus on molecular mechanisms that drive drug resistance in ALL of childhood and discuss the potential of necroptosis activation to eradicate resistant disease.

| S-EPMC6433701 | biostudies-literature

Advanced pancreatic cancer: flourishing novel approaches in the era of biological therapy.

Project description:The progress in the development of systemic treatment for advanced pancreatic cancer (APC) has been slow. The mainstream treatment remains using chemotherapy including gemcitabine, FOLFIRINOX, and nab-paclitaxel. Erlotinib is the only approved biological therapy with marginal benefit. Studies of agents targeting epidermal growth factor receptor, angiogenesis, and RAS signaling have not been satisfying, and the usefulness of targeted therapy in APC is uncertain. Understanding in molecular processes and tumor biology has opened the door for new treatment strategies such as targeting insulin-like growth factor 1 receptor, transforming growth factor ?, phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathway, and Notch pathway. New directions also include the upcoming immunotherapy and many novel agents that act on the microenvironment. The practice of personalized medicine using predictive biomarkers and pharmacogenomics signatures may also enhance the effectiveness of existing treatment. Future treatment approaches may involve comprehensive genomic assessment of tumor and integrated combinations of multiple agents to overcome treatment resistance.

| S-EPMC4153449 | 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