PPAR γ Agonists in Combination Cancer Therapies.

PPARγ Agonists in Combination Cancer Therapies. Curr Cancer Drug Targets. 2019 Dec 08;: Authors: Mrowka P, Glodkowska-Mrowka E Abstract Peroxisome proliferator-activated receptor-gamma (PPARγ) is a nuclear receptor acting as a transcription factor involved in the regulation of energy metabolism, cell cycle, cell differentiation, and apoptosis. These unique properties constitute a strong therapeutic potential that place PPARγ agonists as one of the most interesting and widely studied anticancer molecules. Although PPARγ agonists exert significant, antiproliferative and tumoricidal activity in vitro, their anticancer efficacy in animal models is ambiguous, and their effectiveness in clinical trials in monotherapy is unsatisfactory. However, due to pleiotropic effects of PPARγ activation in normal and tumor cells, PPARγ ligands interact with many antitumor treatment modalities and synergistically potentiate their effectiveness. The most spectacular example is a combination of PPARγ ligands with tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML). In this setting, PPARγ activation sensitizes leukemic stem cells, resistant to any previous form of treatment, to targeted therapy. Thus, this combination is believed to be the first pharmacological therapy able to cure CML patients. Within the last decade, a significant body of data confirming the benefits of the addition of PPARγ ligands to var...
Source: Current Cancer Drug Targets - Category: Cancer & Oncology Authors: Tags: Curr Cancer Drug Targets Source Type: research

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(Centro Nacional de Investigaciones Oncol ó gicas (CNIO)) CNIO researchers destroyed Ewing's sarcoma and chronic myeloid leukaemia tumor cells by using CRISPR to cut out the fusion genes that cause them. For the first time, fusion genes have been selectively and efficiently removed using CRISPR. These genes are attracting a great deal of interest from the research community because they are unique to the tumor cell and are therefore excellent targets for the development of future drugs that only attack the tumor and are harmless for healthy cells.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
Authors: Garcia-Horton A, Lipton JH Abstract With the success of tyrosine kinase inhibitors (TKIs) in achieving next-to-normal overall survival in chronic myeloid leukemia (CML), treatment-free remission (TFR) has become a significant goal in the management of this disease. Discontinuation of therapy is attractive to both patients and physicians because maintaining a stable BCR-ABL transcript level without therapy would imply true operational CML cure. With TFR, patients are not exposed to unknown long-term adverse effects of TKIs and common adverse effects that may affect quality of life. Several factors need to b...
Source: Journal of the National Comprehensive Cancer Network : JNCCN - Category: Cancer & Oncology Tags: J Natl Compr Canc Netw Source Type: research
Authors: Deininger MW, Shah NP, Altman JK, Berman E, Bhatia R, Bhatnagar B, DeAngelo DJ, Gotlib J, Hobbs G, Maness L, Mead M, Metheny L, Mohan S, Moore JO, Naqvi K, Oehler V, Pallera AM, Patnaik M, Pratz K, Pusic I, Rose MG, Smith BD, Snyder DS, Sweet KL, Talpaz M, Thompson J, Yang DT, Gregory KM, Sundar H Abstract Chronic myeloid leukemia (CML) is defined by the presence of Philadelphia chromosome (Ph) which results from a reciprocal translocation between chromosomes 9 and 22 [t(9;22] that gives rise to a BCR-ABL1 fusion gene. CML occurs in 3 different phases (chronic, accelerated, and blast phase) and is usually ...
Source: Journal of the National Comprehensive Cancer Network : JNCCN - Category: Cancer & Oncology Tags: J Natl Compr Canc Netw Source Type: research
AbstractA multicomponent reaction was used as a synthetic strategy to prepare organotin (IV) complexes, 2-amino-3-hydroxypyridine, saliciladehydes 5-R-substituted (H, CH3, OCH3, C(CH)3, F, Cl, Br, I, NO2), and dibutyltin(IV) oxide were used as starting materials. The complexes were analyzed by IR, UV –Visible, MS, NMR of1H,13C,119Sn. The complex3a was structurally identified by X-ray crystallography, which revealed a dimeric arrangement where the tin atom possess a distorted hexacoordinated environment in which the deprotonated phenolic oxygen atoms and the nitrogen atom of the azomethine from the ligand are coordina...
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research
(Hiroshima University) Drugs tackling chronic myelogenous leukemia have completely transformed prognoses of patients over the last couple of decades, with most cases going into remission. But drug resistance can occur, leading to relapses. Targeting the lipids involved in regulating part of a leukemia stem cell's life span offers a potential second route to defeat the disease--and solid tumorous cancers as well.
Source: EurekAlert! - Biology - Category: Biology Source Type: news
ang The EVI1 gene encodes for a transcription factor with two zinc finger domains and is transcriptionally activated in a subset of myeloid leukemias. In leukemia, the transcriptional activation of EVI1 usually results from chromosomal rearrangements. Besides leukemia, EVI1 has also been linked to solid tumors including breast cancer, lung cancer, ovarian cancer and colon cancer. The MDS1/EVI1 gene is encoded by the same locus as EVI1. While EVI1 functions as a transcription repressor, MDS1/EVI1 acts as a transcription activator. The fusion protein encoded by the AML1/MDS1/EVI1 chimeric gene, resulting from chromosomal...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
In conclusion, the cancer cell can escape from immune cells in division stage that suggests the impact of mitosis index for cancer immunotherapy.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
In this study, 394 patients were randomized 1:1 to flumatinib 600 mg once daily (n=196) or imatinib 400 mg once daily (n=198). RESULTS: The rate of major molecular response (MMR) at 6 months (primary end point) was significantly higher with flumatinib than with imatinib (33.7% vs 18.3%, P=0.0006), as was the rate of MMR at 12 months (52.6% vs 39.6%, P=0.0102). At 3 months, the rate of early molecular response (EMR) was significantly higher in patients receiving flumatinib than in those receiving imatinib (82.1% vs 53.3%, P
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
In conclusion, these results revealed that CHK1 is potentially an ideal therapeutic target for the treatment of CML and that CCT245737 should be considered a candidate drug. PMID: 32901871 [PubMed - as supplied by publisher]
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research
Abstract Drug repurposing has lately received increasing interest in several diseases especially in cancers due to its advantages in facilitating the development of new therapeutic strategies, by adopting a cost-friendly approach and avoiding the strict Food and Drug Administration (FDA) regulations. Acriflavine (ACF) is an FDA approved molecule that has been extensively studied since 1912 with antiseptic, trypanocidal, anti-viral, anti-bacterial and anti-cancer effects. ACF has been shown to block the growth of solid and hematopoietic tumor cells. Indeed, ACF acts as an inhibitor of various proteins including DNA...
Source: Current Medicinal Chemistry - Category: Chemistry Authors: Tags: Curr Med Chem Source Type: research
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