The invention includes compositions and methods of treatment of cancers susceptible to treatment with nucleotide analog chemotherapeutic agent, including cancers in which nucleotide analog resistant tumors have developed, including identifying a subject having cancer susceptible to treatment with a nucleotide analog chemotherapeutic agent and a mitotic disruptor/ polo-like kinase (PIk) pathway inhibitor to a subject； and monitoring the subject for a reduction or stabilization of at least one sign or symptom of cancer.
