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Plant-derived natural products have been an important source of several clinically useful anti-cancer agents. Plants continue to play a major role in drug discovery as evidenced by the number of promising new agents in clinical development based on selective activity against cancer-related molecular targets. Due to improvements in tumor targeting technology, some agents which failed in earlier clinical studies are also stimulating renewed interest. We wish to draw the attention of readers to the rapidly evolving recognition that a significant number of natural product drugs/leads are possibly produced by endophytic fungi and microbes residing in the plant tissues. We consider that this area of natural product research should be expanded significantly.