Disclosed is a pharmaceutical composition comprising a mitotic disruptor/polo-like kinase (Plk) pathway inhibitor comprising ON01910, or a derivative thereof, and a nucleotide analog chemotherapeutic agent, wherein the derivative of ON01910 is a compound of the formula (1) as depicted herein,wherein the nucleotide analog chemotherapeutic agent is selected from the group consisting of purine and pyrimidine analogs which interfere with DNA synthesis, andwherein the composition includes a pharmaceutically and physiologically acceptable carrier, in an amount effective for use in a medicament, more preferably for preventing development of nucleotide analog chemotherapeutic agent resistance in a subject having cancer, and most preferably, for use as a medicament for treatment of nucleotide analog chemotherapeutic agent resistant cancer in a subject in need thereof.
