Browse
Submit Data
Databases
API
Help

Dataset Information

14 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

TNBC: Potential Targeting of Multiple Receptors for a Therapeutic Breakthrough, Nanomedicine, and Immunotherapy.

ABSTRACT: Triple-negative breast cancer (TNBC) is a heterogeneous, recurring cancer associated with a high rate of metastasis, poor prognosis, and lack of therapeutic targets. Although target-based therapeutic options are approved for other cancers, only limited therapeutic options are available for TNBC. Cell signaling and receptor-specific targets are reportedly effective in patients with TNBC under specific clinical conditions. However, most of these cancers are unresponsive, and there is a requirement for more effective treatment modalities. Further, there is a lack of effective biomarkers that can distinguish TNBC from other BC subtypes. ER, PR, and HER2 help identify TNBC and are widely used to identify patients who are most likely to respond to diverse therapeutic strategies. In this review, we discuss the possible treatment options for TNBC based on its inherent subtype receptors and pathways, such as p53 signaling, AKT signaling, cell cycle regulation, DNA damage, and programmed cell death, which play essential roles at multiple stages of TNBC development. We focus on poly-ADP ribose polymerase 1, androgen receptor, vascular endothelial growth factor receptor, and epidermal growth factor receptor as well as the application of nanomedicine and immunotherapy in TNBC and discuss their potential applications in drug development for TNBC.

SUBMITTER: Singh DD

PROVIDER: S-EPMC8389539 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Potential Therapeutic Targeting Neurotransmitter Receptors in Diabetes.

Project description:Neurotransmitters are signaling molecules secreted by neurons to coordinate communication and proper function among different sections in the central neural system (CNS) by binding with different receptors. Some neurotransmitters as well as their receptors are found in pancreatic islets and are involved in the regulation of glucose homeostasis. Neurotransmitters can act with their receptors in pancreatic islets to stimulate or inhibit the secretion of insulin (β cell), glucagon (α cell) or somatostatin (δ cell). Neurotransmitter receptors are either G-protein coupled receptors or ligand-gated channels, their effects on blood glucose are mainly decided by the number and location of them in islets. Dysfunction of neurotransmitters receptors in islets is involved in the development of β cell dysfunction and type 2 diabetes (T2D).Therapies targeting different transmitter systems have great potential in the prevention and treatment of T2D and other metabolic diseases.

| S-EPMC9163348 | biostudies-literature

Targeting NK Cell Inhibitory Receptors for Precision Multiple Myeloma Immunotherapy.

Project description:Innate immune surveillance of cancer involves multiple types of immune cells including the innate lymphoid cells (ILCs). Natural killer (NK) cells are considered the most active ILC subset for tumor elimination because of their ability to target infected and malignant cells without prior sensitization. NK cells are equipped with an array of activating and inhibitory receptors (IRs); hence NK cell activity is controlled by balanced signals between the activating and IRs. Multiple myeloma (MM) is a hematological malignancy that is known for its altered immune landscape. Despite improvements in therapeutic options for MM, this disease remains incurable. An emerging trend to improve clinical outcomes in MM involves harnessing the inherent ability of NK cells to kill malignant cells by recruiting NK cells and enhancing their cytotoxicity toward the malignant MM cells. Following the clinical success of blocking T cell IRs in multiple cancers, targeting NK cell IRs is drawing increasing attention. Relevant NK cell IRs that are attractive candidates for checkpoint blockades include KIRs, NKG2A, LAG-3, TIGIT, PD-1, and TIM-3 receptors. Investigating these NK cell IRs as pathogenic agents and therapeutic targets could lead to promising applications in MM therapy. This review describes the critical role of enhancing NK cell activity in MM and discusses the potential of blocking NK cell IRs as a future MM therapy.

| S-EPMC7693637 | biostudies-literature

Nanomedicine for Immunotherapy Targeting Hematological Malignancies: Current Approaches and Perspective.

Project description:Conventional chemotherapy has partial therapeutic effects against hematological malignancies and is correlated with serious side effects and great risk of relapse. Recently, immunotherapeutic drugs have provided encouraging results in the treatment of hematological malignancies. Several immunotherapeutic antibodies and cell therapeutics are in dynamic development such as immune checkpoint blockades and CAR-T treatment. However, numerous problems restrain the therapeutic effectiveness of tumor immunotherapy as an insufficient anti-tumor immune response, the interference of an immune-suppressive bone marrow, or tumoral milieu with the discharge of immunosuppressive components, access of myeloid-derived suppressor cells, monocyte intrusion, macrophage modifications, all factors facilitating the tumor to escape the anti-cancer immune response, finally reducing the efficiency of the immunotherapy. Nanotechnology can be employed to overcome each of these aspects, therefore having the possibility to successfully produce anti-cancer immune responses. Here, we review recent findings on the use of biomaterial-based nanoparticles in hematological malignancies immunotherapy. In the future, a deeper understanding of tumor immunology and of the implications of nanomedicine will allow nanoparticles to revolutionize tumor immunotherapy, and nanomedicine approaches will reveal their great potential for clinical translation.

| S-EPMC8619332 | biostudies-literature

Targeting novel inhibitory receptors in cancer immunotherapy.

Project description:T cells play a critical role in promoting tumor regression in both experimental models and humans. Yet, T cells that are chronically exposed to tumor antigen during cancer progression can become dysfunctional/exhausted and fail to induce tumor destruction. Such tumor-induced T cell dysfunction may occur via multiple mechanisms. In particular, immune checkpoint inhibitory receptors that are upregulated by tumor-infiltrating lymphocytes in many cancers limit T cell survival and function. Overcoming this inhibitory receptor-mediated T cell dysfunction has been a central focus of recent developments in cancer immunotherapy. Immunotherapies targeting inhibitory receptor pathways such as programmed cell death 1 (PD-1)/programmed death ligand 1 and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), alone or in combination, confer significant clinical benefits in multiple tumor types. However, many patients with cancer do not respond to immune checkpoint blockade, and dual PD-1/CTLA-4 blockade may cause serious adverse events, which limits its indications. Targeting novel non-redundant inhibitory receptor pathways contributing to tumor-induced T cell dysfunction in the tumor microenvironment may prove efficacious and non-toxic. This review presents preclinical and clinical findings supporting the roles of two key pathways-T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) and T cell immunoreceptor with Ig and ITIM domain (TIGIT)/CD226/CD96/CD112R-in cancer immunotherapy.

| S-EPMC8045408 | biostudies-literature

Eckol as a Potential Therapeutic against Neurodegenerative Diseases Targeting Dopamine D?/D? Receptors.

Project description:The G protein-coupled receptor (GPCR) family of proteins comprises signaling proteins that mediate cellular responses to various hormones and neurotransmitters, and serves as a prime target for drug discovery. Towards our goal of discovering secondary metabolites from natural sources that can function as neuronal drugs, we evaluated the modulatory effect of eckol on various GPCRs via cell-based functional assays. In addition, we conducted in silico predictions to obtain molecular insights into the functional effects of eckol. Functional assays revealed that eckol had a concentration-dependent agonist effect on dopamine D? and D? receptors. The half maximal effective concentration (EC50) of eckol for the dopamine D? and D? receptors was 48.62 ± 3.21 and 42.55 ± 2.54 µM, respectively, while the EC50 values of dopamine as a reference agonist for these two receptors were 2.9 and 3.3 nM, respectively. In silico studies revealed that a low binding energy in addition to hydrophilic, hydrophobic, ??alkyl, and ??? T-shaped interactions are potential mechanisms by which eckol binds to the dopamine receptors to exert its agonist effects. Molecular dynamics (MD) simulation revealed that Phe346 of the dopamine receptors is important for binding of eckol, similar to eticlopride and dopamine. Our results collectively suggest that eckol is a potential D?/D? agonist for the management of neurodegenerative diseases, such as Parkinson's disease.

| S-EPMC6409773 | biostudies-literature

New Insights and Potential Therapeutic Targeting of CB2 Cannabinoid Receptors in CNS Disorders.

Project description:The endocannabinoid system (ECS) is ubiquitous in most human tissues, and involved in the regulation of mental health. Consequently, its dysregulation is associated with neuropsychiatric and neurodegenerative disorders. Together, the ECS and the expanded endocannabinoidome (eCBome) are composed of genes coding for CB1 and CB2 cannabinoid receptors (CB1R, CB2R), endocannabinoids (eCBs), and the metabolic enzyme machinery for their synthesis and catabolism. The activation of CB1R is associated with adverse effects on the central nervous system (CNS), which has limited the therapeutic use of drugs that bind this receptor. The discovery of the functional neuronal CB2R raised new possibilities for the potential and safe targeting of the ECS for the treatment of CNS disorders. Previous studies were not able to detect CB2R mRNA transcripts in brain tissue and suggested that CB2Rs were absent in the brain and were considered peripheral receptors. Studies done on the role of CB2Rs as a potential therapeutic target for treating different disorders revealed the important putative role of CB2Rs in certain CNS disorders, which requires further clinical validation. This review addresses recent advances on the role of CB2Rs in neuropsychiatric and neurodegenerative disorders, including, but not limited to, anxiety, depression, schizophrenia, Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD) and addiction.

| S-EPMC8778243 | biostudies-literature

Enhancing cancer immunotherapy with nanomedicine.

Project description:Therapeutic targeting of the immune system in cancer is now a clinical reality and marked successes have been achieved, most notably through the use of checkpoint blockade antibodies and chimeric antigen receptor T cell therapy. However, efforts to develop new immunotherapy agents or combination treatments to increase the proportion of patients who benefit have met with challenges of limited efficacy and/or significant toxicity. Nanomedicines - therapeutics composed of or formulated in carrier materials typically smaller than 100 nm - were originally developed to increase the uptake of chemotherapy agents by tumours and to reduce their off-target toxicity. Here, we discuss how nanomedicine-based treatment strategies are well suited to immunotherapy on the basis of nanomaterials' ability to direct immunomodulators to tumours and lymphoid organs, to alter the way biologics engage with target immune cells and to accumulate in myeloid cells in tumours and systemic compartments. We also discuss early efforts towards clinical translation of nanomedicine-based immunotherapy.

| S-EPMC7536618 | biostudies-literature

Therapeutic targeting of TRAIL death receptors.

Project description:The discovery of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) along with its potent and selective antitumor effects initiated a decades-long search for therapeutic strategies to target the TRAIL pathway. First-generation approaches were focused on the development of TRAIL receptor agonists (TRAs), including recombinant human TRAIL (rhTRAIL) and TRAIL receptor-targeted agonistic antibodies. While such TRAIL pathway-targeted therapies showed promise in preclinical data and clinical trials have been conducted, none have advanced to FDA approval. Subsequent second-generation approaches focused on improving upon the specific limitations of first-generation approaches by ameliorating the pharmacokinetic profiles and agonistic abilities of TRAs as well as through combinatorial approaches to circumvent resistance. In this review, we summarize the successes and shortcomings of first- and second-generation TRAIL pathway-based therapies, concluding with an overview of the discovery and clinical introduction of ONC201, a compound with a unique mechanism of action that represents a new generation of TRAIL pathway-based approaches. We discuss preclinical and clinical findings in different tumor types and provide a unique perspective on translational directions of the field.

| S-EPMC9988005 | biostudies-literature

Therapeutic potential of kainate receptors.

Project description:Glutamate receptors are key mediators of brain communication. Among ionotropic glutamate receptors, kainate receptors (KARs) have been least explored and their relevance to pathophysiology is relatively obscure. This is in part due to the relatively low abundance of KARs, the regulatory function in network activity they play, the lack of specific agonists and antagonists for this receptor subtype, as well as to the absence of striking phenotypes in mice deficient in KAR subunits. Nonetheless, it is now well established that KARs are located presynaptically whereby they regulate glutamate and GABA release, and thus, excitability and participate in short-term plasticity. In turn, KARs are also located postsynaptically and their activation contributes to synaptic integration. The development of specific novel ligands is helping to further investigate the contribution of KARs to health and disease. In this review, I summarize current knowledge about KAR physiology and pharmacology, and discuss their involvement in cell death and disease. In addition, I recapitulate the available data about the use of KAR antagonists and receptor subunit deficient mice in experimental paradigms of brain diseases, as well as the main findings about KAR roles in human CNS disorders. In sum, subunit specific antagonists have therapeutic potential in neurodegenerative and psychiatric diseases as well as in epilepsy and pain. Knowledge about the genetics of KARs will also help to understand the pathophysiology of those and other illnesses.

| S-EPMC3430855 | biostudies-literature

Triple-Negative Breast Cancer: Current Understanding and Future Therapeutic Breakthrough Targeting Cancer Stemness.

Project description:Triple-negative breast cancer (TNBC) is cancer that tested as negative for estrogen receptors (ER), progesterone receptors (PR), and excess human epidermal growth factor receptor 2 (HER2) protein which accounts for 15%-20% of all breast cancer cases. TNBC is considered to be a poorer prognosis than other types of breast cancer, mainly because it involves more aggressive phenotypes that are similar to stem cell-like cancer cells (cancer stem cell, CSC). Thus, targeted treatment of TNBC remains a major challenge in clinical practice. This review article surveys the latest evidence concerning the role of genomic alteration in current TNBC treatment responses, current clinical trials and potential targeting sites, CSC and drug resistance, and potential strategies targeting CSCs in TNBC. Furthermore, the role of insulin-like growth factor 1 receptor (IGF-1R) and nicotinic acetylcholine receptors (nAChR) in stemness expression, chemoresistance, and metastasis in TNBC and their relevance to potential treatments are also discussed and highlighted.

| S-EPMC6769912 | 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