One major challenge is the potential for off-target effects, as NHEJ is also essential for normal cellular functions. Inhibiting NHEJ could lead to toxicity in non-cancerous tissues. Furthermore, cancer cells can activate alternative DNA repair pathways, such as Microhomology-Mediated End Joining (MMEJ), leading to resistance against NHEJ-targeted therapies. Thus, a comprehensive understanding of the tumor-specific DNA repair landscape is crucial for effective targeting.
