Abstract:
:Melanoma is the deadliest type of skin cancers, accounting for more than 80% of skin cancer mortality. Although melanoma was known very early in the history of medicine, treatment for this disease had remained largely the same until very recently. Previous treatment options, including removal surgery and systemic chemotherapy, offered little benefit in extending the survival of melanoma patients. However, the last decade has seen breakthroughs in melanoma treatment, which all emerged following new insight into the oncogenic signaling of melanoma. This paper reviewed the evolution of drug targets for melanoma treatment based on the emergence of novel findings in the molecular signaling of melanoma. One of the findings that are most influential in melanoma treatment is that more than 50% of melanoma tumors contain BRAF mutations. This is fundamental for the development of BRAF inhibitors, which is the first group of drugs that significantly improves the overall survival of melanoma patients compared to the traditional chemotherapeutic dacarbazine. More recently, findings of the role of immune checkpoint molecules such as CTLA-4 and PD1/PD-L1 in melanoma biology have led to the development of a new therapeutic category: immune checkpoint inhibitors, which, for the first time in the history of cancer treatment, produced a durable response in a subset of melanoma patients. However, as this paper discussed next, there is still an unmet need for melanoma treatment. A significant population of patients did not respond to either BRAF inhibitors or immune checkpoint inhibitors. Of those patients who gained an initial response from those therapies, a remarkable percentage would develop drug resistance even when MEK inhibitors were added to the treatment. Finally, this paper discusses some possible targets for melanoma treatment.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Tran KB,Buchanan CM,Shepherd PRdoi
10.2174/1381612826666200130091318subject
Has Abstractpub_date
2020-01-01 00:00:00pages
396-414issue
4eissn
1381-6128issn
1873-4286pii
CPD-EPUB-104077journal_volume
26pub_type
杂志文章,评审abstract:BACKGROUND:Antiepileptic treatment strategy plays an important role in the management of intracranial vascular malformations. The intracranial vascular malformations can be divided into cavernous hemangiomas, arteriovenous malformations, developmental venous anomalies and capillary telangiectasias. Seizures and hemorrh...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666171027142718
更新日期:2017-01-01 00:00:00
abstract::Oxidative and nitrosative stress triggers DNA strand breakage, which then activates the nuclear enzyme poly(ADP-ribose) polymerase (PARP). One of the key triggers of DNA single strand breakage in pathophysiological conditions is peroxynitrite, a reactive species produced from the reaction of nitric oxide and superoxid...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206777947579
更新日期:2006-01-01 00:00:00
abstract::Diabetes is an important metabolic disease affecting many organs and systems in the body. The nervous system is one of the body systems affected by diabetes and neuropathic complications are troublesome in diabetic patients with many consequences. As diabetes has deleterious influences almost on bodily systems, an int...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666191014165633
更新日期:2019-01-01 00:00:00
abstract::Packaging small-molecule drugs into nanoparticles improves their bio-availability, bio-compatibility and safety profiles. Multifunctional particles carrying large drug payloads for targeted transport, immune evasion and favourable drug release kinetics at the target site, require a certain minimum size usually 30-300 ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209787002870
更新日期:2009-01-01 00:00:00
abstract::Reducing sugars can react non-enzymatically with amino groups of proteins and lipids to form irreversibly cross-linked macroprotein derivatives called as advanced glycation end products (AGEs). Cross-linking modification of extracellular matrix proteins by AGEs deteriorate their tertiary structural integrity and funct...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666161021155502
更新日期:2017-01-01 00:00:00
abstract::Although the cause of Crohn's disease remains unknown considerable progress has been made in recent years to unravel the pathogenesis of the inflammatory processes seen in chronic idiopathic inflammatory bowel diseases (IBD). Th-1 lymphocytes seem to orchestrate the inflammation through the production of pro-inflammat...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612033391982
更新日期:2003-01-01 00:00:00
abstract::Monocytes are leading component of the mononuclear phagocytic system that play a key role in phagocytosis and removal of several kinds of microbes from the body. Monocytes are bone marrow precursor cells that stay in the blood for a few days and migrate towards tissues where they differentiate into macrophages. Monocy...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190102104642
更新日期:2018-01-01 00:00:00
abstract::Neuroinflammation is a common characteristic of several mental health conditions such as major depression, bipolar disorder, post-traumatic stress disorder (PTSD) and schizophrenia (SCHZ). Inflammatory processes trigger and/or further deteriorate mental functions and are regarded as targets for therapeutic drug develo...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161282210160304112511
更新日期:2016-01-01 00:00:00
abstract::Plasma concentrations of phytosterols and non-cholesterol sterol precursors of cholesterol synthesis have been used as markers of intestinal cholesterol absorption and synthesis in inherited and secondary dyslipidemias and in population-based investigations to evaluate the risk for cardiovascular disease, respectively...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200730220230
更新日期:2020-01-01 00:00:00
abstract::Parkinson's disease (PD) is a common neurodegenerative disorder characterized by cardinal features of tremor, bradykinesia, rigidity and postural instability. In addition to the motor symptoms patients experience cognitive decline eventually resulting in severe disability. Pathologically PD is characterized by neurode...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043453162
更新日期:2004-01-01 00:00:00
abstract::Protein kinases are potential targets of drugs to treat many human diseases. Intensive efforts have been made to develop protein kinase inhibitors, but a major challenge is achieving specificity. Exploiting regulatory elements outside the ATP binding pocket, such as the substrate binding site, may provide an alternati...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212800672741
更新日期:2012-01-01 00:00:00
abstract::P-Glycoprotein (P-gp) is a 170-kDa transmembrane glycoprotein that works as an efflux pump and confers multidrug resistance (MDR) in normal tissues and tumors, including nervous tissues and brain tumors. In the developing telencephalon, the endothelial expression of P-gp, and the subcellular localization of the transp...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200318130625
更新日期:2020-01-01 00:00:00
abstract::Urological cancer refers to cancer in organs of the urinary system and the male reproductive system. It mainly includes prostate cancer, bladder cancer, renal cancer, etc., seriously threatening patients' survival. Although there are many advances in the treatment of urological cancer, approved targeted therapies ofte...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612826666200403131514
更新日期:2020-01-01 00:00:00
abstract::The cardiovascular system exhibits significant daily rhythms in physiologic processes (heart rate, blood pressure, cardiac contractility and function), and molecular gene and protein expression. An increasing number of clinical and experimental studies demonstrate the circadian system is an important underlying mechan...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150706105926
更新日期:2015-01-01 00:00:00
abstract::Growth and metastasis of lung cancer requires a sequence of events, which alter the ability of neoplastic cells to adhere to themselves, to normal surrounding cells, or to the extracellular matrix. Interactions between cells are primarily mediated by four types of structures in the plasma membrane: gap junctions, tigh...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208785740162
更新日期:2008-01-01 00:00:00
abstract::Erectile function is determined by tight regulation of relaxation or contraction of corpus cavernosal smooth muscle, which is the result of a long and complex chain of molecular events. Control of erectile function resides in signaling pathways of the central and peripheral nervous system, as well as intracellular eve...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161205774913426
更新日期:2005-01-01 00:00:00
abstract::Gene delivery, a process of introducing foreign functional nucleic acids into target cells, has proven to be a very promising tool for inducing specific gene expression in host cells. Many different technologies have been developed for efficient gene delivery. Among them, electroporation has been adopted in gene deliv...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666151027152121
更新日期:2015-01-01 00:00:00
abstract::Heat shock proteins (HSPs) are involved in a number of cellular processes, including cell cycle, growth, and survival, apoptosis, stress responses, angiogenesis, and oncogenesis. Among the characterized HSPs, the molecular chaperone HSP90 has emerged as an exciting molecular target for cancer therapy since its discove...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:
更新日期:2013-01-01 00:00:00
abstract::The development of radioligands to image beta-amyloid (A beta) plaques and neurofibrillary tangles (NFTs) in vivo in the aging human brain is an important and active area of radiopharmaceutical design. When used in combination with positron emission tomography (Pet) or single photon emission computed tomography (spect...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043384772
更新日期:2004-01-01 00:00:00
abstract::Thrombotic events occurring in either arteries or veins are the primary causes of fatal perioperative cardiovascular events. Risk factors for deep vein thrombosis, several of which are evidently associated with specific surgical procedures, are quite different from those for arterial thrombosis (e.g., aging or atheros...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612820666140204102044
更新日期:2014-01-01 00:00:00
abstract::Understanding of the roles of RNAs within the cell has changed and expanded dramatically during the past few years. Based on fundamentally new insights it is now increasingly possible to employ RNAs as highly valuable tools in molecular biology and medicine. At present, the most important therapeutic strategies are ba...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210791792813
更新日期:2010-01-01 00:00:00
abstract::The chemical structure of polyphenols consisting of aromatic rings, capable of quenching free radicals, makes them ideal candidates to protect against oxidation. Polyphenols are present in a variety of foods including grapes, berries, dark chocolate, coffee and tea to mention a few. A number of studies have shown that...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170329144307
更新日期:2017-01-01 00:00:00
abstract::The final aim/target of Pharmaceutical Sciences is to design successful dosage forms for effective therapy, considering individual patient needs and compliance. Development of new drug entities, particularly using peptides and proteins, is growing in importance and attracting increased interest, as they are specifical...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207779313795
更新日期:2007-01-01 00:00:00
abstract::Despite the development of strong antibiotics, the pneumonia death is increasing all over the world in these decades. Among the people who died of pneumonia, the majority were 65 years old or over. Although pneumonia is recently categorized into several entities, aspiration pneumonia includes all entities. Therefore, ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990567
更新日期:2014-01-01 00:00:00
abstract::The disappointing results in long-term survival of patients affected by non-small cell lung cancer (NSCLC) may be attributed, at least in part, to the lack of knowledge on the way by which genetic characteristics in normal and neoplastic cells affect responsiveness as well as metabolism of chemotherapy and new targete...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113196660756
更新日期:2014-01-01 00:00:00
abstract::The rise of multi-drug resistant and extensively drug resistant M. tuberculosis around the world poses a great threat to human health, and necessitates development of new, effective and inexpensive anti-tubercular agents. The availability of knowledge on molecular biology of M. tuberculosis infection coupled with whol...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612819666131118165427
更新日期:2014-01-01 00:00:00
abstract::Non-enzymatic modification of proteins by reducing sugars, a process that is also known as Maillard reaction, leads to the formation of advanced glycation end products (AGEs) in vivo. There is a growing body of evidence that formation and accumulation of AGEs progress during normal aging, and at an extremely accelerat...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208784139747
更新日期:2008-01-01 00:00:00
abstract::The intracellular hydric balance is an essential process of mammalian cells. The water movement across cell membranes is driven by osmotic and hydrostatic forces and the speed of this process is dependent on the presence of specific aquaporin water channels. Since the molecular identification of the first water channe...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207781368738
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:Central serous chorioretinopathy (CSC) is the fourth most frequent retinal disorder in terms of prevalence. It typically occurs in young subjects and affects men more often than women. CSC is characterized by serous retinal detachment (SRD) involving mainly the macular area. The clinical course is usually se...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190123165914
更新日期:2018-01-01 00:00:00
abstract::Methicillin-resistant Staphylococcus aureus (MRSA) remains the single biggest challenge in infectious disease in the civilized world. Moreover, vancomycin resistance is also spreading, leading to fears of untreatable infections as were common in ancient times. Molecular microbiology and bioinformatics have revealed ma...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150310101851
更新日期:2015-01-01 00:00:00