The Adverse Impact of Tyrosine Kinase Inhibitors on Wound Healing and Repair

Area of Science:

• Oncology
• Vascular Biology
• Regenerative Medicine

Background:

• Tyrosine kinase inhibitors (TKIs) are vital cancer therapeutics, often acting via antiangiogenic mechanisms.
• Angiogenesis, the formation of new blood vessels, is essential for effective wound healing.
• The antiangiogenic effects of TKIs raise concerns about their potential to impede wound repair.

Purpose of the Study:

• To review all FDA-approved TKIs and assess their implications for wound healing and repair.
• To identify the specific molecular targets of TKIs that contribute to impaired wound healing.
• To synthesize evidence regarding the clinical impact of TKIs on surgical wound outcomes.

Main Methods:

• Comprehensive analysis of all 63 FDA-approved TKIs.
• Identification of TKIs with documented effects on wound healing and repair.
• Review of safety data, preclinical studies, case reports, and clinical trials.

Main Results:

• Evidence for wound healing implications was found in 24 of the 63 approved TKIs.
• Inhibition of vascular endothelial growth factor receptors (VEGFRs) is the primary mechanism for impaired healing, with EGFR and PDGFR also implicated.
• Data indicates TKIs can cause delayed or impaired wound healing, necessitating treatment discontinuation before and after surgery.

Conclusions:

• TKIs can significantly impact wound healing, primarily through VEGFR inhibition.
• Current safety guidelines recommend pausing TKI therapy around surgical interventions to ensure adequate wound healing.
• Awareness and proactive management of TKI-associated wound complications are crucial for patient safety as TKI use expands.