Drug resistance.

Drug resistance. Adv Exp Med Biol. 2014;844:303-16 Authors: Tomasetti C Abstract Drug resistance is a fundamental problem in the treatment of cancer since cancer that becomes resistant to the available drugs may leave the patient with no therapeutic alternatives. In this chapter, we consider the dynamics of drug resistance in blood cancer and the related issue of the dynamics of cancer stem cells. After describing the main types of chemotherapeutic agents available for cancer treatment, we review the different mechanisms of drug resistance development. Various mathematical models of drug resistance found in the literature are then reviewed. Given the well-known hierarchy of the hematopoietic system, it is critical to focus on those cells that have the ability to self-renew, since these will be the only cells able to induce long-term drug resistance. Thus, a recent mathematical model taking into account the complex dynamics of the leukemic stem-like cells is described. The chapter closes with a few applications of this model to chronic myeloid leukemia. PMID: 25480648 [PubMed - in process]
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research

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The introduction of the drug imatinib in 2001 revolutionized the treatment of a type of cancer called chronic myelogenous leukemia. In more than 80% of people with CML who received the drug, the disease went into complete remission.However, in most people with chronic myelogenous leukemia, cancerous stem cells remain in the body for years after their cancer has gone into remission. If treatment with imatinib or another similar medication is stopped — and in some cases, even while treatment continues — the leukemia stem cells can cause cancer to recur.Now, in experiments in mice as well as isolated human cancer ...
Source: UCLA Newsroom: Health Sciences - Category: Universities & Medical Training Source Type: news
We report the case of a aCML patient successfully treated with AZA. A 66-year-old man with no remarkable medical history was admitted to our hospital because of leukocytosis. We diagnosed his disease as aCML and administered hydroxyurea (HU) and AZA. After four courses of AZA, his blood cell values improved, and he no longer needed transfusions and was able to stop HU. He continued receiving AZA without any severe complications. This is the first report that AZA is effective for the treatment of aCML.
Source: Indian Journal of Cancer - Category: Cancer & Oncology Authors: Source Type: research
Natural killer (NK) cells are large granular lymphocytes involved in our defense against certain virus-infected and malignant cells. In contrast to T cells, NK cells elicit rapid anti-tumor responses based on signals from activating and inhibitory cell surface receptors. They also lyse target cells via antibody-dependent cellular cytotoxicity, a critical mode of action of several therapeutic antibodies used to treat cancer. A body of evidence shows that NK cells can exhibit potent anti-tumor activity against chronic myeloid leukemia (CML), acute myeloid leukemia (AML), and myelodysplastic syndromes (MDS). However, disease-...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
ConclusionsDLI was associated with a durable efficacy and low toxicity in pediatric patients with hematologic malignancies. However, larger studies and standardized approaches are required to identify the outcome predictors of this treatment modality.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest.
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
Abstract Chronic myeloid leukaemia (CML) is a paradigm of precision medicine, being one of the first cancers to be treated with targeted therapy. This has revolutionised CML therapy and patient outcome, with high survival rates. However, this now means an ever-increasing number of patients are living with the disease on life-long tyrosine kinase inhibitor (TKI) therapy, with most patients anticipated to have near normal life expectancy. Unfortunately, in a significant number of patients, TKIs are not curative. This low-level disease persistence suggests that despite a molecularly targeted therapeutic approach, the...
Source: Biochemical Society Transactions - Category: Biochemistry Authors: Tags: Biochem Soc Trans Source Type: research
Authors: Mirza MAB, Guru SA, Abdullah SM, Rizvi A, Saxena A Abstract Background: Chronic myeloid leukaemia (CML) is a myeloproliferative disorder categorized by malignant transformation of a single stem cell of hematopoietic cells. microRNAs (miRNAs) belong to transcription regulators in hematopoiesis and their altered expression associates with pathogenesis of CML. Aim: Current study aimed to access the miR-21 expression profile in CML patients and therapy response as well as its prognostic significance. Methods: 100 CML cases, 100 controls were included in study and miR-21 expression was analyzed. Overall 9.22 me...
Source: Asian Pacific Journal of Cancer Prevention - Category: Cancer & Oncology Tags: Asian Pac J Cancer Prev Source Type: research
Abstract Mutation and translocation of fibroblast growth factor receptors often lead to aberrant signaling and cancer. This work focuses on the t(8;22)(p11;q11) chromosomal translocation which creates the BCR-FGFR1 fusion protein. This fusion occurs in stem cell leukemia/lymphoma, which can progress to atypical chronic myeloid leukemia, acute myeloid leukemia, or B-Cell lymphoma. This work focuses on biochemical characterization of BCR-FGFR1 and identification of novel therapeutic targets. The tyrosine kinase activity of FGFR1 is required for biological activity as shown using transformation assays, IL-3 independe...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
Publication date: Available online 10 August 2019Source: Seminars in Cancer BiologyAuthor(s): Peter Valent, Irina Sadovnik, Gregor Eisenwort, Harald Herrmann, Karin Bauer, Niklas Mueller, Wolfgang R. Sperr, Daniel Wicklein, Udo SchumacherAbstractThe development of a myeloid neoplasm is a step-wise process that originates from leukemic stem cells (LSC) and includes pre-leukemic stages, overt leukemia and a drug-resistant terminal phase. Organ-invasion may occur in any stage, but is usually associated with advanced disease and a poor prognosis. Sometimes, extra-medullary organ invasion shows a metastasis-like or even sarcoma...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
Abstract Chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell neoplasm characterized by an uncontrolled proliferation of moderately and well differentiated cells of the granulocytic lineage. LW-213, a newly synthesized flavonoid compound, was found to exert antitumor effects against breast cancer through inducing G2/M phase arrest. We investigated whether LW-213 exerted anti-CML effects and the underlying mechanisms. We showed that LW-213 inhibited the growth of human CML cell lines K562 and imatinid-resistant K562 (K562r) in dose- and time-dependent manners with IC50 values at the low μmol/L leve...
Source: Acta Pharmacologica Sinica - Category: Drugs & Pharmacology Authors: Tags: Acta Pharmacol Sin Source Type: research
Conclusion: Eradicating CML-LSCs via anti-CD26-4-1BB-CAR T cells is not applicable, and optimized design or alternative target is needed. PMID: 31303072 [PubMed - as supplied by publisher]
Source: Immunopharmacology and Immunotoxicology - Category: Allergy & Immunology Tags: Immunopharmacol Immunotoxicol Source Type: research
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