Abstract：
:Mechanistic insights of cancer immunology have led to the development of immune checkpoint blockade therapy (ICBT), which has elicited a remarkable clinical response in some cancer patients. Increasing evidence suggests that activation of oncogenic pathways, such as RAS/RAF/MAPK and PI3K signaling, impairs the antitumor immune response. Such oncogenic signaling, in turn, activates many inhibitory factors, including expression of immune checkpoint genes-allowing active infiltration of immunosuppressive cells into the tumor environment and inducing resistance against T-cell killing. In preclinical tumor models, effective targeting of oncogenic pathways has enhanced the response to ICBT. Ongoing clinical trials are now evaluating combination therapy (i.e., the use of oncogenic pathway inhibitors in combination with ICBT). However, more translational and clinical research is needed, to optimize ICBT doses and sequence, minimize toxicity, and assess the impact on study participants of certain genetic backgrounds. Also, it is crucial to understand whether wild-type tumors with elevated oncogenic signaling will respond to combination therapy. Insights gained through current and future translational studies will provide the scientific premise and rationale to target 1 or more oncogenic pathways in ICBT-resistant tumors, thus enabling more human patients to benefit from combination therapy.
journal_name
Pharmacol Therjournal_title
Pharmacology & therapeuticsauthors
Zhao X,Subramanian Sdoi
10.1016/j.pharmthera.2017.07.004subject
Has Abstractpub_date
2018-01-01 00:00:00pages
76-84eissn
0163-7258issn
1879-016Xpii
S0163-7258(17)30164-Xjournal_volume
181pub_type
杂志文章,评审abstract：:Granulocytes are defined as the population of granulated white blood cells (eosinophils, neutrophils, and basophils). These cells are involved in inflammation and contribute to the pathogenesis of allergic and inflammatory diseases. Inflammation is induced by the release of mediators from granulocytes recruited to or ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2005.03.008
更新日期：2005-09-01 00:00:00
abstract：:Evidence that the delta opioid receptor (DOR) is an attractive target for the treatment of brain disorders has strengthened in recent years. This receptor is broadly expressed in the brain, binds endogenous opioid peptides, and shows as functional profile highly distinct from those of mu and kappa opioid receptors. Ou...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2013.06.003
更新日期：2013-10-01 00:00:00
abstract：:Pulmonary hypertension (PH) in newborns and infants can present in its idiopathic form or complicate a long list of other diseases. Most of these conditions are either pulmonary or cardiovascular in origin. In the present review our current knowledge regarding pathophysiology, structural changes, diagnosis, and availa...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2007.03.006
更新日期：2007-06-01 00:00:00
abstract：:The integration of retroviral DNA appears to be obligatory for the efficient replication of retroviruses in their respective host cells. During a natural infection, integration takes place in a process that includes biochemically and temporally discrete steps. These are: (1) the removal of two nucleotides from the 3' ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(94)90062-0
更新日期：1994-01-01 00:00:00
abstract：:The small heat shock proteins (HSPs) HSP20, HSP27 and alphaB-crystallin are chaperone proteins that are abundantly expressed in smooth muscles are important modulators of muscle contraction, cell migration and cell survival. This review focuses on factors regulating expression of small HSPs in smooth muscle, signaling...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2008.04.005
更新日期：2008-07-01 00:00:00
abstract：:Cancer promotion, development, and malignant transformation is greatly influenced by cell-to-cell interactions in a complex tissue microenvironment. Cancer and stromal cells secrete soluble factors, as well as deport membrane-encapsulated structures, which actively contribute and mediate cell-to-cell interaction withi...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2021.107806
更新日期：2021-01-16 00:00:00
abstract：:Aside from their pharmacokinetic properties, e.g. their speed of action and the duration of residual effects, benzodiazepines are still considered as equivalent in terms of their effects on cognition. Here we review evidence suggesting that certain benzodiazepines, especially lorazepam, differ in a number of respects,...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2010.01.004
更新日期：2010-04-01 00:00:00
abstract：:The PI3K/Akt/mTOR pathway is the most frequently known activated aberrant pathway in human cancers. Pathologic activation can occur at multiple levels along the signaling pathway by a variety of mechanisms, including point mutations, amplifications, and inactivation of tumor suppressor genes. This pathway is also a kn...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2014.09.006
更新日期：2015-02-01 00:00:00
abstract：:Dysregulation of inflammation is central to the pathogenesis of innumerable human diseases. Understanding and tracking the critical events in inflammation are crucial for disease monitoring and pharmacological drug discovery and development. Recent progress in molecular imaging has provided novel insights into spatial...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2012.05.006
更新日期：2012-08-01 00:00:00
abstract：:The importance of regular administration of antiplatelet drugs in patients suffering from coronary artery disease stands on firm grounds, as large meta-analyses have shown these therapies to drastically reduce the risk of death. Although the current guidelines published jointly by the American Heart Association, the A...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2009.03.019
更新日期：2009-08-01 00:00:00
abstract：:Nitric oxide (NO) formed via endothelial NO synthase (eNOS) and neuronal NO synthase (nNOS) plays crucial roles in the regulation of blood flow through vasodilatation and decreased vascular resistance in various organs and tissues. NO derived from eNOS also contributes to the inhibition of platelet aggregation, adhesi...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2010.04.009
更新日期：2010-09-01 00:00:00
abstract：:Minor groove binders are small molecules that form strong complexes with the minor groove of DNA. There are several structural types of which distamycin and netropsin analogues, oligoamides built from heterocyclic and aromatic amino acids, and bis-amidines separated by aromatic and heterocyclic rings are of particular...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2013.03.002
更新日期：2013-07-01 00:00:00
abstract：:The smooth muscle of the normal bladder wall must have some specific properties. It must be very compliant and able to reorganise itself during filling and emptying to accommodate the change in volume without generating any intravesical pressure, but whilst maintaining the normal shape of the bladder. It must be capab...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(97)00038-7
更新日期：1997-08-01 00:00:00
abstract：:G-protein-coupled receptors (GPCRs) comprise the largest family of transmembrane receptors in the human genome that respond to a plethora of signals, including neurotransmitters, peptide hormones, and odorants, to name a few. They couple to second messenger signaling cascade mechanisms via heterotrimeric G-proteins. R...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(01)00160-7
更新日期：2001-11-01 00:00:00
abstract：:Diabetes is a debilitating disease characterized by chronic hyperglycemia and is often associated with obesity. With diabetes and obesity incidence on the rise, it is imperative to develop novel therapeutics that will not only lower blood glucose levels, but also combat the associated obesity. The G protein-coupled re...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2012.05.009
更新日期：2012-09-01 00:00:00
abstract：:Initially regarded as "epigenetic modifiers" acting predominantly through chromatin remodeling via histone acetylation, HDACIs, alternatively referred to as lysine deacetylase or simply deacetylase inhibitors, have since been recognized to exert multiple cytotoxic actions in cancer cells, often through acetylation of ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2014.04.004
更新日期：2014-09-01 00:00:00
abstract：:gamma-Aminobutyric acid (GABA)A receptors for the inhibitory neurotransmitter GABA are likely to be found on most, if not all, neurons in the brain and spinal cord. They appear to be the most complicated of the superfamily of ligand-gated ion channels in terms of the large number of receptor subtypes and also the vari...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(95)02043-8
更新日期：1996-01-01 00:00:00
abstract：:A number of neuronal functions, including synaptic plasticity, depend on proper regulation of synaptic proteins, many of which can be rapidly regulated by phosphorylation. Neuronal activity controls the function of these synaptic proteins by exquisitely regulating the balance of various protein kinase and protein phos...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2006.06.003
更新日期：2006-12-01 00:00:00
abstract：:Cardiovascular diseases (CVDs) remain the leading cause of death in the developed countries. Taking into account the mounting evidence about the role of cytochrome P450 (CYP) enzymes in cardiovascular physiology, CYP polymorphisms can be considered one of the major determinants of individual susceptibility to CVDs. On...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2009.12.002
更新日期：2010-03-01 00:00:00
abstract：:The pharmaceutical industry offers the world's population alleviation and cure from a variety of medical conditions, while also contributing to the economic performance of many countries. The potential importance of these characteristics have made the industry an area of intense debate, criticism and praise. This revi...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(95)00002-x
更新日期：1995-05-01 00:00:00
abstract：:Aquaporin (AQP) water and solute channels have basic physiological functions throughout the human body. AQP-facilitated water permeability across cell membranes is required for rapid reabsorption of water from pre-urine in the kidneys and for sustained near isosmolar water fluxes e.g. in the brain, eyes, inner ear, an...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2015.08.002
更新日期：2015-11-01 00:00:00
abstract：:We have concentrated on how SCE is measured, how it correlates with other measures of cellular damage, and how SCE can be used as a tool to study cell cycle kinetics. We have not discussed the biological significance of SCEs, i.e. why they occur spontaneously, and what role, if any, in cellular preservation they play....
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(89)90030-2
更新日期：1989-01-01 00:00:00
abstract：:Astroglial cells express neurotrophic and/or neurite growth-promoting factors, including (a) peptide growth factors (e.g. nerve growth factors, ciliary neuronotrophic factor, fibroblast growth factor), (b) neurotransmitters (such as glutamate, neuropeptide Y), (c) cell adhesion molecules (e.g. N-CAM) and (d) extracell...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(94)00047-7
更新日期：1995-01-01 00:00:00
abstract：:Hepatic methionine adenosyltransferase (MAT) deficiency is caused by mutations in the human MAT1A gene that abolish or reduce hepatic MAT activity that catalyzes the synthesis of S-adenosylmethionine from methionine and ATP. This genetic disorder is characterized by isolated persistent hypermethioninemia in the absenc...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(99)00047-9
更新日期：2000-01-01 00:00:00
abstract：:Infection or sterile inflammation triggers site-specific attraction of leukocytes. Leukocyte recruitment is a process comprising several steps orchestrated by adhesion molecules, chemokines, cytokines and endogenous regulatory molecules. Distinct adhesive interactions between endothelial cells and leukocytes and signa...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2014.11.008
更新日期：2015-03-01 00:00:00
abstract：:Liver parenchyma shows a remarkable heterogeneity of the hepatocytes along the porto-central axis with respect to ultrastructure and enzyme activities resulting in different cellular functions within different zones of the liver lobuli. According to the concept of metabolic zonation, the spatial organization of the va...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(92)90055-5
更新日期：1992-01-01 00:00:00
abstract：:The vascular system develops during embryonic development by at least two distinct processes; vasculogenesis is the development of blood vessels from in situ differentiating angioblasts and angiogenesis is the sprouting of capillaries from pre-existing vessels. The molecular mechanisms involved in the regulation of th...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(91)90066-u
更新日期：1991-01-01 00:00:00
abstract：:Progress in methods of investigating endothelial function in humans has led to the demonstration that endothelial dysfunction is an early process involved in the pathophysiology of cardiovascular diseases, and represents a new independent therapeutic target that may help to improve patient health. The administration o...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2011.03.015
更新日期：2011-07-01 00:00:00
abstract：:Protein kinases recognize and bind to specific amino acid sequences on their protein substrates. These sequences can be readily identified using combinatorial peptide libraries. Unfortunately, conventional peptide libraries are not designed to identify subtle structural factors that can dramatically enhance enzyme aff...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(02)00187-0
更新日期：2002-02-01 00:00:00
abstract：:Although potent effects of psychoactive drugs on circadian rhythms were first described over 30 years ago, research into the reciprocal relationship between the reward system and the circadian system - and the impact of this relationship on addiction - has only become a focus in the last decade. Nonetheless, great pro...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2018.03.003
更新日期：2018-08-01 00:00:00
