Major Research Findings

Bosutinib is a tyrosine kinase inhibitor that has shown promising results in the treatment of various cancers, including thyroid papillary carcinoma and chronic myeloid leukemia (CML). 16 It was found to inhibit the growth, invasion, and migration of thyroid papillary carcinoma cells and promote their apoptosis, thereby reducing their malignant behavior. 16 . Additionally, bosutinib demonstrated the ability to inhibit autophagy in these cells through the SIK2-mTOR-ULK1 signaling pathway, further contributing to its anticancer effects. 16 .

Bosutinib has also been studied for its potential impact on heart function in healthy individuals. A study found that therapeutic and supratherapeutic doses of bosutinib did not prolong the corrected QT interval (QTc), a measure of heart rhythm, in healthy adults. 21 This suggests that bosutinib is unlikely to cause significant cardiac abnormalities in patients receiving therapeutic doses.

Research has highlighted the potential for renal toxicity associated with bosutinib, particularly in patients with hypertension. 1 Studies have shown a significant decrease in estimated glomerular filtration rate (eGFR) in CML patients taking bosutinib, especially those also receiving renin-angiotensin-aldosterone system inhibitors (RAASi). 1 . Therefore, close monitoring of renal function is crucial for patients on bosutinib therapy.

Bosutinib has also been investigated in the context of its potential impact on platelet function. Some studies found that bosutinib can increase platelet aggregation in whole blood, indicating a possible risk for thrombotic events. 14 However, other studies have shown that bosutinib does not impair platelet function when used in therapeutically relevant concentrations. 14 Further research is necessary to fully understand its effects on platelet function.

In the context of CML treatment, bosutinib has shown promise as a second-line therapy for patients who do not respond well to initial treatments. 18 Studies have found that bosutinib, while slightly more expensive than some other second-line TKIs, can be considered a cost-effective option. 18 However, it’s important to remember that bosutinib has a specific safety profile and its use should be carefully considered in patients with pre-existing conditions.

Benefits and Risks

Benefits Summary

Bosutinib has shown potential as a treatment for various cancers, including thyroid papillary carcinoma and CML, by effectively inhibiting cancer cell growth and promoting their death. 16 It has also been shown to be safe for heart function in healthy adults. 21 In the context of CML treatment, bosutinib appears to be a cost-effective option as a second-line therapy. 18

Risks Summary

The most notable risk associated with bosutinib is its potential for renal toxicity, particularly in patients with hypertension or those receiving RAASi. 1 While further research is necessary, some studies suggest that bosutinib may increase platelet aggregation, potentially increasing the risk of blood clots. 14

Comparison of Studies

Commonalities

Across multiple studies, bosutinib has demonstrated consistent anticancer activity, particularly in the context of CML. 8 It has been found to improve overall survival rates in patients with CML, particularly those receiving allogeneic stem cell transplantation (allo-SCT). 8 Additionally, studies have shown that bosutinib can be used to treat patients who are resistant or intolerant to other TKIs. 4

Differences

While studies show similar anticancer activity, different mechanisms of action have been suggested for bosutinib. For instance, one study found that bosutinib inhibits autophagy in thyroid papillary carcinoma cells via the SIK2-mTOR-ULK1 signaling pathway. 16 Another study demonstrated that bosutinib can promote differentiation in leukemia cells, potentially through an off-target effect that is independent of Src family kinases. 7 These discrepancies highlight the need for further investigation to better understand the mechanisms underlying bosutinib’s therapeutic effects.

Consistency and Contradictions

While the majority of research suggests that bosutinib is an effective treatment for CML, further research is necessary to fully understand its mechanisms of action. There are some discrepancies in the reported effects of bosutinib on platelet function, and some studies indicate that it can increase platelet aggregation, while others suggest no impairment of platelet function. 14 More research is needed to clarify these inconsistencies.

Real-World Applications and Caveats

Bosutinib is a valuable treatment option for CML patients, but close monitoring of renal function is crucial, especially in patients with hypertension or those receiving RAASi. 1 Patients should be aware of potential side effects and discuss their medical history and any relevant concerns with their healthcare provider before starting bosutinib therapy.

Limitations of Current Research

The body of research on bosutinib is continually growing, but there are still knowledge gaps. Further investigation is needed to fully understand the mechanisms underlying bosutinib’s effects on different types of cancer cells, as well as its potential interactions with other medications. 15

Future Research Directions

Future research should focus on further elucidating the mechanisms of action for bosutinib, particularly its effects on different cell types and its interactions with other drugs. 9 Additionally, more research is needed to assess bosutinib’s effectiveness in combination therapies and its long-term safety profiles. 7

Conclusion

Bosutinib is a promising tyrosine kinase inhibitor that has shown significant anticancer activity in various types of cancer. 16 However, it’s essential to be aware of its potential for renal toxicity, especially in patients with hypertension or those receiving RAASi. 1 Patients should discuss any potential concerns with their healthcare providers before starting bosutinib therapy. Further research is needed to gain a deeper understanding of bosutinib’s mechanisms of action, its safety profile, and its potential benefits in combination therapies. 7