0
selected
-
1.
Novel therapeutic approaches in chronic myeloid leukemia.
Özgür Yurttaş, N, Eşkazan, AE
Leukemia research. 2020;:106337
Abstract
The tyrosine kinase inhibitors (TKIs) have revolutionized the management of chronic myeloid leukemia (CML) and BCR-ABL1 inhibitors form the mainstay of CML treatment. Although patients with CML generally do well under TKI therapy, there is a subgroup of patients who are resistant and/or intolerant to TKIs. In these group of patients, there is the need of additional treatment strategies. In this review, we provide an update on the current knowledge of these novel treatment approaches that can be used alone and/or in combination with TKIs.
-
2.
Targeted Molecular Therapeutic Options for Hepatocellular Carcinoma.
Sridhar, S, Sharma, I, Sankpal, UT, Ghabach, B, Narra, K, Neerukonda, L, Basha, R
Critical reviews in oncogenesis. 2020;(1):47-55
Abstract
Liver cancer is the 6th leading cause of cancer related deaths in the US even though it ranks 14th in incidence. More men are diagnosed with liver cancer than women, and the number of projected deaths among men (20,020) is almost double that among women (10,140) in the US. Infections like hepatitis and metabolic conditions like obesity are believed to be major risk factors for the onset of liver cancer. Hepatocellular carcinoma (HCC), the most common type of liver cancer, accounts for 75% of all cases. Chemotherapy has not been effective in treating HCC. Targeted therapies are being used in advanced HCC patients due to a better survival and less side effects when compared to traditional chemotherapy. Therapeutic agents targeting the regulators of growth factor signaling pathways and the mediators of downstream signaling-for example, inhibitors of the tyrosine kinase receptor-are used as targeted molecular therapies. Kinase inhibitors that modulate growth signals, such as sorafenib and lenvatinib, are commonly employed in targeted molecular therapy for HCC patients. This review covers these agents, highlighting modes of action and providing details on clinical trials.
-
3.
The concept of disease modification.
Cross, JH, Lagae, L
European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society. 2020;:43-46
Abstract
Traditionally treatment of epileptic seizures has been symptomatic, namely medication has been targeted at raising the threshold to the occurrence of epileptic seizures. This has had little impact on the rate of drug resistance over time, or impact on comorbidities such as learning and behaviour particularly in the early onset epilepsies. The advent of advanced neuroimaging and genomics has revealed the cause of the epilepsy in a much higher percentage, and advanced our knowledge as to the underlying pathophysiology. This has given us the opportunity to turn to the possibility of interventional treatment, targeting the underlying cause, and consequently the possibility of changing the natural history of disease. Here we review the options open to us, and the evidence to date.
-
4.
Molecular targeted therapies: Ready for "prime time" in biliary tract cancer.
Lamarca, A, Barriuso, J, McNamara, MG, Valle, JW
Journal of hepatology. 2020;(1):170-185
Abstract
The prognosis for patients with biliary tract cancers (cholangiocarcinoma and gallbladder cancer) is poor, while the incidence of these cancers is increasing. Most patients are diagnosed with advanced disease when treatment options are limited to palliative approaches, mainly focused on chemotherapy. In recent years, novel treatment targets of relevance to biliary tract cancers, mainly present in patients with intrahepatic cholangiocarcinoma, have been identified and are rapidly changing the field. These include fibroblast growth factor receptor (FGFR) fusions and isocitrate dehydrogenase (IDH)-1 and -2 mutations which are each present in around 10-20% of patients with intrahepatic cholangiocarcinoma. In addition, inhibition of other pathways/molecules is currently being explored, including human epidermal growth factor receptor (HER) family members, the Wnt pathway, neurotropic tyrosine kinase receptor (NTRK) fusions and BRAF mutations. The IDH1 inhibitor ivosidenib has already been tested in a phase III clinical trial in pretreated cholangiocarcinoma and showed benefit in terms of progression-free survival. Multiple FGFR inhibitors have consistently shown high response rates in phase II/III trials, especially for patients harbouring FGFR2 fusions. Herein, we provide an overview of the status of targeted therapies in biliary tract cancers, discussing the current clinical development of IDH and FGFR inhibitors in detail, as well as reviewing current caveats and future steps.
-
5.
Immunotherapy and potential molecular targets for the treatment of pituitary adenomas resistant to standard therapy: a critical review of potential therapeutic targets and current developments.
Maghathe, T, Miller, WK, Mugge, L, Mansour, TR, Schroeder, J
Journal of neurosurgical sciences. 2020;(1):71-83
Abstract
INTRODUCTION Pituitary adenomas (PAs) are primary central nervous system (CNS) tumors, accounting for as much as 25% of intracranial neoplasms. Although existing remedies show success in treating most PAs, treatment of invasive and non-functioning PAs, in addition to functioning PAs unresponsive to standard therapy, remains challenging. With the continually increasing understanding of biochemical pathways involved in tumorigenesis, immunotherapy stands as a promising alternative therapy for pituitary tumors that are resistant to standard therapy. EVIDENCE ACQUISITION A literature search was conducted of the PubMed database for immunotherapies of PAs. The search yielded a total of 2621 articles, 26 of which were included in our discussion. EVIDENCE SYNTHESIS Several pathologically expressed molecules could potentially serve as promising targets of current or future immunotherapies for PAs. Programmed death ligand-1, matrix metalloproteinases, EpCAM (Trop1) and Trop2, cancer-testis antigen MAGE-A3, epidermal growth factor receptor (EGFR), folate receptor alpha, vascular endothelial growth factor, and galectin-3 have all been implicated as crucial factors involved with tumor survival and invasion. Inhibition of these pathways may prove efficacious in the management of invasive and treatment-resistant PAs. CONCLUSIONS Rapid advancements in tumor immunology may increase the probability of successful treatment of PAs by exploitation of the normal immune response or by targeting novel proteins. Current research on many of the targets reviewed in this article are successfully being utilized to manage various neoplastic disease including CNS tumors. These therapies may eventually play a key role in the treatment of PAs that do not respond to standard therapy.
-
6.
Exosome: A Review of Its Classification, Isolation Techniques, Storage, Diagnostic and Targeted Therapy Applications.
Zhang, Y, Bi, J, Huang, J, Tang, Y, Du, S, Li, P
International journal of nanomedicine. 2020;:6917-6934
Abstract
Exosomes are nano-sized small extracellular vesicles secreted by cells, carrying nucleic acids, proteins, lipids and other bioactive substances to play a role in the body's physiological and pathological processes. Compared to synthetic carriers such as liposomes and nanoparticles, the endogeneity and heterogeneity of exosomes give them extensive and unique advantages in the field of disease diagnosis and treatment. However, the storage stability, low yield, low purity, and weak targeting of exosomes limit its clinical application. For this reason, further exploration is needed to optimize the above problems and facilitate future functional studies of exosomes. In this paper, the origin, classification, preparation and characterization, storage stability and applications of exosome delivery system are summarized and discussed by searching a large number of literatures.
-
7.
Beta Thalassemia: New Therapeutic Options Beyond Transfusion and Iron Chelation.
Motta, I, Bou-Fakhredin, R, Taher, AT, Cappellini, MD
Drugs. 2020;(11):1053-1063
-
-
Free full text
-
Abstract
Hemoglobinopathies are among the most common monogenic diseases worldwide. Approximately 1-5% of the global population are carriers for a genetic thalassemia mutation. The thalassemias are characterized by autosomal recessive inherited defects in the production of hemoglobin. They are highly prevalent in the Mediterranean, Middle East, Indian subcontinent, and East and Southeast Asia. Due to recent migrations, however, the thalassemias are now becoming more common in Europe and North America, making this disease a global health concern. Currently available conventional therapies in thalassemia have many challenges and limitations. A better understanding of the pathophysiology of β-thalassemia in addition to key developments in optimizing transfusion programs and iron-chelation therapy has led to an increase in the life span of thalassemia patients and paved the way for new therapeutic strategies. These can be classified into three categories based on their efforts to address different features of the underlying pathophysiology of β-thalassemia: correction of the globin chain imbalance, addressing ineffective erythropoiesis, and improving iron overload. In this review, we provide an overview of the novel therapeutic approaches that are currently in development for β-thalassemia.
-
8.
Targeting endothelial exosomes for the prevention of cardiovascular disease.
Jia, G, Sowers, JR
Biochimica et biophysica acta. Molecular basis of disease. 2020;(8):165833
Abstract
Exosomes are small lipid bilayer-enclosed 30-140 nm diameter vesicles formed from endosomes. Exosomes are secreted by various cell types including endothelial cells, immune cells and other cardiovascular tissues, and they can be detected in plasma, urine, cerebrospinal fluid, as well as tissues. Exosomes were initially regarded as a disposal mechanism to discard unwanted materials from cells. Recent studies suggest that exosomes play an important role in mediating of intercellular communication through the delivery and transport of cellular components such as nucleic acids, lipids, and proteins and thus regulate cardiovascular disease. Further, the underlying mechanisms by which abnormally released exosomes promote cardiovascular disease are not well understood. This review highlights recent studies involving endothelial exosomes, gives a brief overview of exosome biogenesis and release, isolation and identification of exosomes, and provides a contemporary understanding of the endothelial exosome pathophysiology and potential therapeutic strategies.
-
9.
[Acquired Drug Resistance Mechanism of Osimertinib in the Targeted Therapy of Non-small Cell Lung Cancer].
Zhao, Z, Ni, Y, Li, L, Xin, T
Zhongguo fei ai za zhi = Chinese journal of lung cancer. 2020;(4):274-281
Abstract
While treating cancer, epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) still faces inevitable drug resistance. Investigations into the mechanisms which foster resistance to EGFR-TKI has led to the discovery of novel biomarkers and drug targets, and in turn has enabled the development of third-generation TKIs and proposals for rational therapeutic combinations. The threonine-to-methionine substitution mutation at position 790 (T790M) is clinically validated to engender refractoriness to first- and second-generation TKI, and is a standard-of-care predictive biomarker used in therapeutic stratification. For patients who are T790M-negative, cytotoxic chemotherapy or protracted EGFR-TKI treatment are acceptable treatment standards after disease progression, although combinations of targeted therapies and checkpoint blockade immunotherapy may offer promising alternatives in the future. Among T790M-positive patients, the third-generation EGFR-TKI, osimertinib, has shown superiority over both platinum-doublet chemotherapy and first-generation EGFR-TKI in randomized clinical trials. This article appraises the key literature on the contemporary management of non-small cell lung cancer patients with acquired resistance to EGFR-TKIs, and envisions future directions in translational and clinical research.
-
10.
Natural Compounds in Prostate Cancer Prevention and Treatment: Mechanisms of Action and Molecular Targets.
Fontana, F, Raimondi, M, Marzagalli, M, Di Domizio, A, Limonta, P
Cells. 2020;(2)
Abstract
Prostate cancer (PCa) represents a major cause of cancer mortality among men in developed countries. Patients with recurrent disease initially respond to androgen-deprivation therapy, but the tumor eventually progresses into castration-resistant PCa; in this condition, tumor cells acquire the ability to escape cell death and develop resistance to current therapies. Thus, new therapeutic approaches for PCa management are urgently needed. In this setting, natural products have been extensively studied for their anti-PCa activities, such as tumor growth suppression, cell death induction, and inhibition of metastasis and angiogenesis. Additionally, numerous studies have shown that phytochemicals can specifically target the androgen receptor (AR) signaling, as well as the PCa stem cells (PCSCs). Interestingly, many clinical trials have been conducted to test the efficacy of nutraceuticals in human subjects, and they have partially confirmed the promising results obtained in vitro and in preclinical models. This article summarizes the anti-cancer mechanisms and therapeutic potentials of different natural compounds in the context of PCa prevention and treatment.