scholarly journals Analysis of a case with disappearance of the primary gastrointestinal stromal tumor and progressive liver metastases under long-term treatment with tyrosine kinase inhibitors

2009 ◽  
Vol 27 (2) ◽  
pp. 213-218 ◽  
Author(s):  
Silke Cameron ◽  
Theodoros Savvoukidis ◽  
Thomas Armbrust ◽  
Florian Haller ◽  
Julia Kitz ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Liver Metastases ◽  
Gastrointestinal Stromal Tumor ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Term Treatment ◽  
Stromal Tumor ◽  
Long Term Treatment

scholarly journals BCR-ABL1 tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia

2017 ◽  
Vol 24 (6) ◽  
pp. 433-452 ◽  
Author(s):  
Sandra Cuellar ◽  
Michael Vozniak ◽  
Jill Rhodes ◽  
Nicholas Forcello ◽  
Daniel Olszta
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Drug Interactions ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Term Treatment ◽  
Patient Centered ◽  
Long Term Treatment

The management of chronic myeloid leukemia with BCR-ABL1 tyrosine kinase inhibitors has evolved chronic myeloid leukemia into a chronic, manageable disease. A patient-centered approach is important for the appropriate management of chronic myeloid leukemia and optimization of long-term treatment outcomes. The pharmacist plays a key role in treatment selection, monitoring drug–drug interactions, identification and management of adverse events, and educating patients on adherence. The combination of tyrosine kinase inhibitors with unique safety profiles and individual patients with unique medical histories can make managing treatment difficult. This review will provide up-to-date information regarding tyrosine kinase inhibitor-based treatment of patients with chronic myeloid leukemia. Management strategies for adverse events and considerations for drug–drug interactions will not only vary among patients but also across tyrosine kinase inhibitors. Drug–drug interactions can be mild to severe. In instances where co-administration of concomitant medications cannot be avoided, it is critical to understand how drug levels are impacted and how subsequent dose modifications ensure therapeutic drug levels are maintained. An important component of patient-centered management of chronic myeloid leukemia also includes educating patients on the significance of early and regular monitoring of therapeutic milestones, emphasizing the importance of adhering to treatment in achieving these targets, and appropriately modifying treatment if these clinical goals are not being met. Overall, staying apprised of current research, utilizing the close pharmacist–patient relationship, and having regular interactions with patients, will help achieve successful long-term treatment of chronic myeloid leukemia in the age of BCR-ABL1 tyrosine kinase inhibitors.

Successful use of long-term follow-up in patients with chronic myeloid leukemia with a deep molecular response at reduced doses of 2nd generation tyrosine kinase inhibitors: clinical cases and literature review

2020 ◽  
Vol 92 (7) ◽  
pp. 90-94
Author(s):  
M. A. Gurianova ◽  
E. Yu. Chelysheva ◽  
O. A. Shukhov ◽  
A. G. Turkina
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Term Treatment ◽  
Molecular Response ◽  
Long Term Treatment ◽  
Deep Molecular Response

Therapy with tyrosine kinase inhibitors (TKI) allows to achieve a deep molecular response in 6070% of patients with chronic myeloid leukemia (CML). According to the current guidelines CML patients receive a long-term treatment with TKI in standard dose. The frequently observed adverse effects (AE) of TKI therapy are mostly dose-dependent. A new treatment approach with TKI use in reduced dose is desirable for the CML patients with existing AE or with a high risk of AE occurrence. We report the two cases of successful long-term treatment of CML patients with reduced doses of second generation TKIs. The aim of the TKI dose reduction was to reduce the clinical manifestations of drug toxicities and to prevent the AE.

scholarly journals The mechanisms of sensitization of gastrointestinal stromal tumor cells to DNA topoisomerase II inhibitors

2019 ◽  
Vol 100 (2) ◽  
pp. 245-251
Author(s):  
P D Dunaev ◽  
A R Galembikova ◽  
S V Boichuk
Keyword(s):  
Tyrosine Kinase ◽  
Gastrointestinal Stromal Tumor ◽  
Tumor Cells ◽  
Tyrosine Kinase Inhibitors ◽  
Receptor Tyrosine Kinase ◽  
Topoisomerase Ii ◽  
Kinase Inhibitors ◽  
Stromal Tumor ◽  
Topoisomerase Ii Inhibitors ◽  
Receptor Tyrosine Kinase Inhibitors

Aim. To examine the ability of receptor tyrosine kinase inhibitors to modulate gastrointestinal stromal tumor cells sensitivity to DNA topoisomerase II inhibitors. Methods. The following receptor tyrosine kinase inhibitors were used in the present study - imatinib, crizotinib, cabozantinib and sunitinib. An ability of the named medications to sensitize gastrointestinal stromal tumor cells to DNA topoisomerase II inhibitor (doxorubicin) was examined by using an MTS-based colorimetric assay. The expression of apoptotic, DNA damage and repair markers was assessed with western blotting by using the corresponding monoclonal antibodies. Proliferative activity was examined in a real-time by utilizing an iCELLigence system (ACEA Biosciences Inc., USA). Results. We found that all above-mentioned receptor tyrosine kinase inhibitors were able to sensitize gastrointestinal stromal tumor cells to topoisomerase II inhibitors. This leads to the decrease of proliferative activity of tumors cells and enhancement of apoptotic cell death. Importantly, this effect was observed in imatinib-resistant gastrointestinal stromal tumor cells. One of the possible molecular mechanisms responsible for sensitization of these cells to topoisomerase II inhibitors was the ability of the target medications to inhibit the homologous recombination. This is evidenced by substantial decrease of Rad51 recombinase expression as a result of receptor tyrosine kinase inhibitor effect on the cells with DNA damage caused by topoisomerase II inhibitors. Conclusion. Receptor tyrosine kinase inhibitors are able to sensitize imatinib-resistant gastrointestinal stromal tumor cells to topoisomerase II inhibitors by inhibiting DNA homologous recombination.

scholarly journals Antimetabolic cooperativity with the clinically approved kidrolase and tyrosine kinase inhibitors to eradicate cml stem cells

2020 ◽  
Author(s):  
Anne Trinh ◽  
Raeeka Khamari ◽  
Quentin Fovez ◽  
François-Xavier Mahon ◽  
Béatrice Turcq ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Death ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Atp Synthesis ◽  
Term Treatment ◽  
Glutamine Metabolism ◽  
Apoptotic Pathway ◽  
Long Term Treatment

AbstractLong-term treatment with tyrosine kinase inhibitors (TKI) represents an effective treatment for chronic myeloid leukemia (CML) and discontinuation of TKI therapy is now proposed to patient with deep molecular responses. However, evidence demonstrating that TKI are unable to fully eradicate dormant leukemic stem cells indicate that new therapeutic strategies are needed to prevent molecular relapses. We investigated the metabolic pathways responsible for CML surviving to Imatinib exposure and its potential therapeutic utility to improve the efficiency of TKI against CML stem cells. Using complementary cell-based techniques, we demonstrated that TKI suppressed glycolysis in a large panel of BCR-ABL1 + cell lines as well as in primary CD34+ stem-like cells from CML patients. However, compensatory glutamine-dependent mitochondrial oxidation supported ATP synthesis and CML cell survival. Glutamine metabolism was inhibited by L-asparaginases such as Kidrolase without inducing predominant CML cell death. Clinically relevant concentrations of TKI render CML progenitors and stem cells susceptible to Kidrolase. The combination of TKI with L-asparaginase reactivated the intinsic apoptotic pathway leading to efficient CML cell death. Thus, targeting glutamine metabolism with the clinically-approved drug Kidrolase, in combination with TKI that suppress glycolysis represents an effective and widely applicable therapeutic strategy for eradicating CML stem cells.

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