Search results for " Targeted therapy"
showing 10 items of 198 documents
Bioactive pyrrole-based compounds with target selectivity
2020
The discovery of novel synthetic compounds with drug-like properties is an ongoing challenge in medicinal chemistry. Natural products have inspired the synthesis of compounds for pharmaceutical application, most of which are based on N-heterocyclic motifs. Among these, the pyrrole ring is one of the most explored heterocycles in drug discovery programs for several therapeutic areas, confirmed by the high number of pyrrole-based drugs reaching the market. In the present review, we focused on pyrrole and its hetero-fused derivatives with anticancer, antimicrobial, and antiviral activities, reported in the literature between 2015 and 2019, for which a specific target was identified, being resp…
Advances in Targeting Signal Transduction Pathways
2012
// James A. McCubrey 1 , Linda S. Steelman 1 , William H. Chappell 1 , Lin Sun 1,2 , Nicole M. Davis 1 , Stephen L. Abrams 1 , Richard A. Franklin 1 , Lucio Cocco 3 , Camilla Evangelisti 4 , Francesca Chiarini 4 , Alberto M. Martelli 3,4 , Massimo Libra 5 , Saverio Candido 5 , Giovanni Ligresti 5 , Grazia Malaponte 5 , Maria C. Mazzarino 5 , Paolo Fagone 5 , Marco Donia 5 , Ferdinando Nicoletti 5 , Jerry Polesel 6 , Renato Talamini 6 , Jorg Basecke 7 , Sanja Mijatovic 8 , Danijela Maksimovic-Ivanic 8 , Michele Milella 9 , Agostino Tafuri 10 , Joanna Dulinska-Litewka 11 , Piotr Laidler 11 , Antonio B. D’Assoro 12 , Lyudmyla Drobot 13 , Kazuo Umezawa 14 , Giuseppe Montalto 15 , Melchiorre Cer…
FGFR a promising druggable target in cancer: Molecular biology and new drugs.
2017
Abstract: Introduction: The Fibroblast Growth Factor Receptor (FGFR) family consists of Tyrosine Kinase Receptors (TKR) involved in several biological functions. Recently, alterations of FGFR have been reported to be important for progression and development of several cancers. In this setting, different studies are trying to evaluate the efficacy of different therapies targeting FGFR. Areas Covered: This review summarizes the current status of treatments targeting FGFR, focusing on the trials that are evaluating the FGFR profile as inclusion criteria: Multi-Target, Pan-FGFR Inhibitors and anti-FGF (Fibroblast Growth Factor)/FGFR Monoclonal Antibodies. Expert opinion: Most of the TKR share …
Current questions for the treatment of advanced gastric cancer.
2013
Abstract Background Gastric cancer remains a major health problem worldwide. Treatment of advanced gastric cancer is controversial and there is no standard regimen for first- or second-line chemotherapy (CT). This review aims to give an overview of the hot topics concerning treatment, prognostic factors and new strategies in advanced gastric cancer. Material and methods Seven questions of special clinical interest have been formulated previously to the literature review. With the aim of answering each of these questions, a specific search of the relevant trials and meta-analyses published or communicated from 1990 to date was performed. Results Patients treated with CT have a survival benef…
Therapeutic targets for overactive bladder other than smooth muscle
2015
For a long time, our concepts of regulation of urinary bladder function in health and disease as well as of the target structures of therapeutics have focused on detrusor smooth muscle cells. However, other structures including urothelium, afferent nerves and bladder blood vessels may also be important in pathophysiology and its treatment.Based on a selective review of literature, we discuss the role of urothelium, afferent nerve fibers and bladder blood vessels in bladder pathophysiology and as targets for treatment.There is solid evidence now that multiple anatomical structures within the urinary bladder contribute to the regulation of its function and hence may be targets for established…
The emerging role of miRNA-132/212 cluster in neurologic and cardiovascular diseases: Neuroprotective role in cells with prolonged longevity
2021
Abstract miRNA-132/212 are small regulators of gene expression with a function that fulfills a vital function in diverse biological processes including neuroprotection of cells with prolonged longevity in neurons and the cardiovascular system. In neurons, miRNA-132 appears to be essential for controlling differentiation, development, and neural functioning. Indeed, it also universally promotes axon evolution, nervous migration, plasticity as well, it is suggested to be neuroprotective against neurodegenerative diseases. Moreover, miRNA-132/212 disorder leads to neural developmental perturbation, and the development of degenerative disorders covering Alzheimer’s, Parkinson’s, and epilepsy’s …
Mutations and Deregulation of Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascades Which Alter Therapy Response.
2012
The Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascades are often activated by genetic alterations in upstream signaling molecules such as receptor tyrosine kinases (RTK). Certain components of these pathways, RAS, NF1, BRAF, MEK1, DUSP5, PP2A, PIK3CA, PIK3R1, PIK3R4, PIK3R5, IRS4, AKT, NFKB1, MTOR, PTEN, TSC1, and TSC2 may also be activated/inactivated by mutations or epigenetic silencing. Upstream mutations in one signaling pathway or even in downstream components of the same pathway can alter the sensitivity of the cells to certain small molecule inhibitors. These pathways have profound effects on proliferative, apoptotic and differentiation pathways. Dysregulation of components of these cas…
Presenilin is the molecular target of acidic γ-secretase modulators in living cells.
2012
The intramembrane-cleaving protease γ-secretase catalyzes the last step in the generation of toxic amyloid-β (Aβ) peptides and is a principal therapeutic target in Alzheimer's disease. Both preclinical and clinical studies have demonstrated that inhibition of γ-secretase is associated with prohibitive side effects due to suppression of Notch processing and signaling. Potentially safer are γ-secretase modulators (GSMs), which are small molecules that selectively lower generation of the highly amyloidogenic Aβ42 peptides but spare Notch processing. GSMs with nanomolar potency and favorable pharmacological properties have been described, but the molecular mechanism of GSMs remains uncertain an…
Targeted Therapy Modulates the Secretome of Cancer-Associated Fibroblasts to Induce Resistance in HER2-Positive Breast Cancer
2021
The combination of trastuzumab plus pertuzumab plus docetaxel as a first-line therapy in patients with HER2-positive metastatic breast cancer has provided significant clinical benefits compared to trastuzumab plus docetaxel alone. However, despite the therapeutic success of existing therapies targeting HER2, tumours invariably relapse. Therefore, there is an urgent need to improve our understanding of the mechanisms governing resistance, so that specific therapeutic strategies can be developed to provide improved efficacy. It is well known that the tumour microenvironment (TME) has a significant impact on cancer behaviour. Cancer-associated fibroblasts (CAFs) are essential components of the…
Management of metabolic adverse events of targeted therapies and immune checkpoint inhibitors in cancer patients: an Associazione Italiana Oncologia …
2020
The growing insights in the next-generation immunotherapy and the state-of-the-art advancement in targeted-agents significantly improved clinical outcome of cancer patients by pointing towards a unexplored Achilles' heel. Novel toxicity profiles have been uncovered, representing unmet medical needs. Thus, a panel of expert provide comprehensive pharmacological and clinical evidence, to provide a patient-tailored approach to metabolic adverse events associated with novel anti-cancer treatments. Prompted by the need of a multidisciplinary cooperation, a working group of Associazione Italiana Oncologia Medica (AIOM), Associazione Medici Diabetologi (AMD) and Societa Italiana Farmacologia (SIF)…