decitabine + crizotinib

Decitabine + crizotinib is an experimental combination therapy consisting of two small molecule drugs with distinct mechanisms of action. Decitabine is a DNA methyltransferase inhibitor (a hypomethylating agent) that induces DNA hypomethylation, leading to reactivation of silenced genes and apoptosis in malignant cells. Crizotinib is a tyrosine kinase inhibitor targeting anaplastic lymphoma kinase (ALK), ROS1, and MET kinases, blocking oncogenic signaling pathways involved in cell proliferation and survival. This combination has been investigated preclinically for synergistic effects in ALK-positive anaplastic large-cell lymphoma (ALCL), where it demonstrated enhanced efficacy over monotherapy by suppressing the emergence of resistant tumor cells and inducing deeper inhibition of oncogenic signaling[1]. The rationale for this combination lies in preventing or overcoming resistance to single-agent targeted therapies.