Major Research Findings

Imatinib is a tyrosine kinase inhibitor that has been revolutionizing the treatment of chronic myeloid leukemia (CML). 17 , 10 , 22 , 19 , 5 , 1 , 8 , 20 , 21 , 18 , 9 , 13 , 14 , 4 , 3 These studies have investigated its effectiveness and various aspects of its application. Several studies have reported its anti-cancer effects, however, there are also reports of side effects and development of resistance.

For example, 17 showed that combining synthesized ZnO/CNT@Fe₃O₄ nanocomposite with Imatinib reduced the survival rate of CML-derived K562 cells. This is believed to be due to reactive oxygen species-mediated apoptosis induction. The improved cytotoxicity in the presence of a well-known autophagy inhibitor indicates that the apoptotic effect of this treatment is enhanced through autophagy suppression. Investigation of the molecular mechanisms responsible for the growth-suppressive effect of ZnO/CNT@Fe₃O₄-plus-Imatinib suggested that up-regulation of SIRT1 halted cell cycle progression by increasing the expression of p21 and p27 cyclin-dependent kinase inhibitors. It is important to note that this study, for the first time, reported that either direct or indirect suppression of c-Myc resulted in enhanced anti-leukemic efficacy. This suggests that c-Myc overexpression plays a contributing role in attenuating the effectiveness of ZnO/CNT@Fe₃O₄-Imatinib in K562 cells. The promising effect of ZnO/CNT@Fe₃O₄ in potentiating the anti-cancer effects of Imatinib in K562 cells suggests that nanocomposites could be utilized as a tool for combined-strategy treatment. However, further in vivo experiments are necessary to provide insights into the safety and efficacy of this nanocomposite.

10 demonstrates that cannabidiol (CBD), through TRPV2, inhibits cell proliferation and cell cycle in CML cells. CBD promoted mitochondrial dysfunction and mitophagy as shown by mitochondrial mass reduction and up-regulation of several mitophagy markers. These effects were associated with changes in the expression of octamer-binding transcription factor 4 and PU.1 markers regulated during cellular differentiation. Interestingly, a synergistic effect by combining CBD with the standard drug imatinib was found, and imatinib-resistant cells remain susceptible to CBD effects. Therefore, targeting TRPV2 using CBD, through the activation of mitophagy and the reduction in stemness, could be a promising strategy to enhance conventional therapy and improve the prognosis of CML patients.

7 reports that Imatinib induces diastolic dysfunction and ventricular early-repolarization delay in halothane-anesthetized dogs. Imatinib decreased the amplitude of peak -dP/dt, indicating suppression of isovolumetric relaxation, while no significant change was detected in other phases. Imatinib prolonged QTc and J-T_peakc without altering T_peak-T_end, indicating an increase in net inward current, which leads to intracellular Ca²⁺ overload. Thus, Imatinib suppressed ventricular active relaxation and early repolarization, suggesting an association with mitochondrial dysfunction-associated inhibition of ATP production. Since these findings were also reported for dasatinib, sunitinib, and lapatinib, they could represent a common cardiac phenotype of tyrosine kinase inhibitors in vivo.

15 shows that sulfasalazine synergistically enhances the inhibitory effects of imatinib against hepatocellular carcinoma (HCC) cells by targeting NFκB, BCR/ABL, and PI3K/AKT signaling pathway-related proteins. When compared to either medication alone, the combined use of imatinib and sulfasalazine enhanced the inhibition of HCC cell proliferation and extended induction of apoptosis. These findings suggest that sulfasalazine synergistically potentiates the antitumor effects of imatinib.

1 reports that metformin exerts antileukemic effects by modulating lactate metabolism and overcomes imatinib resistance in chronic myelogenous leukemia. Metformin inhibits the growth of imatinib-resistant cell lines and peripheral blood mononuclear cells isolated from patients who relapsed following imatinib treatment. Metformin exerted these antiproliferative effects by inhibiting MCT1 and MCT4, leading to the inhibition of lactate export. These results delineate the molecular mechanisms underlying metabolic reprogramming leading to secondary imatinib resistance and the potential of metformin as a therapeutic option in CML.

Benefits and Risks

Benefits Summary

Imatinib is considered a viable treatment option for the treatment of chronic myeloid leukemia (CML). Several studies show that Imatinib effectively suppresses the growth of CML cells and induces apoptosis. 17 , 10 , 19 , 1 , 3 Additionally, 15 reports that combining Imatinib with sulfasalazine inhibits the growth of hepatocellular carcinoma (HCC) cells and promotes apoptosis. Furthermore, 17 indicates that combining Imatinib with ZnO/CNT@Fe₃O₄ nanocomposite reduces the survival rate of CML cells. These findings suggest that Imatinib could be an effective drug for treating various types of cancers, including CML and HCC.

Risks Summary

Several side effects associated with Imatinib have been reported. 7 shows that Imatinib can delay heart contraction and early repolarization. 14 reports that Imatinib can potentially cause thrombosis. Furthermore, 21 indicates that the concentration of Imatinib in the blood and genetic polymorphisms can affect its effectiveness. These findings suggest that it is important to be cautious about the potential risks of side effects when using Imatinib.

Comparison Between Studies

Commonalities

Many studies report that Imatinib suppresses the growth of cancer cells and induces apoptosis. It has also been shown that Imatinib can be combined with other drugs to enhance its effects. However, research also indicates that Imatinib poses risks, such as side effects and the development of resistance.

Differences

The effectiveness of Imatinib varies depending on the type of cancer, dosage, and other medications used in conjunction. While 7 suggests that Imatinib may affect the heart, other research does not report any effects on the heart.

Consistency and Contradictions

The research on the effects of Imatinib is still ongoing, and therefore there is still some inconsistency and contradiction in its effects. However, it is believed to be an effective drug for treating cancers such as CML. Further research is needed to better understand the effects of Imatinib.

Applying Research Findings in Daily Life

It is important to take Imatinib according to your doctor's instructions. If you experience any side effects while taking Imatinib, consult your doctor immediately. Imatinib is not suitable for everyone. If you are considering taking Imatinib, consult with your doctor.

Limitations of Current Research

The research on the effects of Imatinib is not yet fully developed. In particular, the mechanisms of side effects and resistance to Imatinib are not fully understood. More research is necessary to further evaluate the safety and effectiveness of Imatinib.

Future Research Directions

To further understand the effects of Imatinib, the following research is needed:

• Understanding the mechanisms of side effects and resistance to Imatinib.
• Research on the dosage of Imatinib and its combination with other drugs.
• Research on the long-term effects of Imatinib.

Conclusion

Imatinib is considered an effective drug for treating cancers, such as CML. However, research also indicates that Imatinib poses risks, such as side effects and the development of resistance. When using Imatinib, it is important to be cautious about the potential risks of side effects. More research is necessary to further understand the effects of Imatinib. If you are considering taking Imatinib, consult with your doctor.