Researchers in Singapore find common therapeutic vulnerability for a genetically diverse and deadly

(Duke-NUS Medical School) Scientists and clinicians from Duke-NUS Medical School, the Agency for Science, Technology and Research's (A*STAR's) Genome Institute of Singapore (GIS), and the Singapore General Hospital (SGH), have devised a novel drug combination that could treat a particularly deadly form of leukaemia, known as blast crisis (BC) chronic myeloid leukaemia (CML). The team has also developed strategies that may identify patients with early stage or chronic phase (CP) CML who are at increased risk of developing BC, and potentially preventing disease progression.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news

Related Links:

Today I'll point out an example of drug reuse and autophagy upregulation. The processes of autophagy are responsible for recycling molecular waste and broken cellular structures. Autophagy is upregulated in response to stress placed upon cells, whether by heat, cold, lack of nutrients, a toxic local environment, and so forth. This is beneficial to tissue function, health, and longevity, and thus there is considerable interest in the research community in producing therapies that boost the operation of autophagy. This hasn't made a great deal of progress towards the clinic, but nonetheless in any of the sizable databases of...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
This study demonstrated the critical role of the ABL gene in maintaining CML cell survival and tumorigenicity in vitro and in vivo. ABL gene editing-based therapy might provide a potential strategy for imatinib-insensitive or resistant CML patients.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Revised Funding Information.
Source: Supportive Care in Cancer - Category: Cancer & Oncology Source Type: research
The advent of tyrosine kinase inhibitors (TKIs) targeted therapy revolutionized the treatment of chronic myeloid leukemia (CML) patients. However, cardiotoxicity associated with these targeted therapies puts the cancer survivors at higher risk. Ponatinib is a third-generation TKI for the treatment of CML patients having gatekeeper mutation T315I, which is resistant to the first and second generation of TKIs, namely, imatinib, nilotinib, dasatinib, and bosutinib. Multiple unbiased screening from our lab and others have identified ponatinib as most cardiotoxic FDA approved TKI among the entire FDA approved TKI family (total 50+).
Source: International Journal of Cardiology - Category: Cardiology Authors: Source Type: research
Source: Nutrition and Cancer - Category: Cancer & Oncology Authors: Source Type: research
lçın AS Abstract Flavonoids are phenolic substances with chemo-preventive and chemotherapeutic properties. They are widely found in fruits and vegetables. The polyphenols quercetin and curcumin have antioxidant, anti-inflammatory, anti-carcinogenic, and pro-apoptotic properties. They were successfully used against different human cancers, especially chronic myeloid leukemia cancer cells. We have previously investigated anti-proliferative and apoptotic effects of quercetin and curcumin combination in K562 cells. Our data showed that they had beneficial synergistic effects. Based on these findings, we aimed ...
Source: Nutrition and Cancer - Category: Cancer & Oncology Authors: Tags: Nutr Cancer Source Type: research
Circular RNAs (circRNAs), which act as initiators and promoters of various diseases, were thought to be mostly noncoding RNAs (ncRNAs) in eukaryotes, until recent studies confirmed that some circRNAs have the function of encoding proteins. Accumulating research findings have proved that dysregulation of circRNAs is associated with the developmental process of multiple cancers. circHIPK3, an example of circRNA, is frequently expressed in many diseases, such as diabetes, age-related cataract, idiopathic pulmonary fibrosis, preeclampsia, osteoblasts, and retinal vascular dysfunction, leading to disease development and progres...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
The objective is to evaluate the long-term efficacy and the occurrence of vascular occlusion with second-generation BCR-ABL TKIs compared with imatinib in patients with CML. Three scientific databases, a clinical registry and abstracts from congress were searched to identify all randomized controlled trials that compared a second-generation BCR-ABL TKI to imatinib in patients with CML. Outcomes extracted were overall survival, major molecular response and complete cytogenetic response, arterial occlusive events and venous thromboembolism. These data were synthesized by odds ratios using a fixed-effect model. This meta-anal...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
In this study, we treated human hematopoietic stem and progenitor cells (HSPCs) harvested from a patient with chronic myelogenous leukemia (CML) with gemcitabine/carboplatin. Thereafter, scRNA-seq was performed to distinguish transcriptional effects induced by gemcitabine/carboplatin. Gene expression was calculated and evaluated among cells within and between samples compared to untreated cells. Cell cycle analysis showed that the treatments effectively decrease cell proliferation, indicated by the proportion of cells in the G2M-phase dropping from 35% in untreated cells to 14.3% in treated cells. Clustering and t-SNE show...
Source: Genes - Category: Genetics & Stem Cells Authors: Tags: Article Source Type: research
Abstract Patients with chronic myeloid leukemia (CML) often require lifelong therapy with ABL1 tyrosine kinase inhibitors (TKIs) due to a persisting TKI-resistant population of leukemic stem cells (LSCs). From transcriptome profiling, we show integrin-linked kinase (ILK), a key constituent of focal adhesions, is highly expressed in TKI-nonresponsive patient cells and their LSCs. Genetic and pharmacological inhibition of ILK impaired the survival of nonresponder patient cells, sensitizing them to TKIs, even in the presence of protective niche cells. Furthermore, ILK inhibition eliminated TKI-refractory LSCs from pa...
Source: Cell Stem Cell - Category: Stem Cells Authors: Tags: Cell Stem Cell Source Type: research
More News: Cancer | Cancer & Oncology | Chronic Leukemia | Chronic Myeloid Leukaemia | Genetics | Hospitals | Leukemia | Science | Singapore Health