These Milestones celebrate two decades of breakthroughs in basic, translational and clinical research which have revolutionised our understanding and management of cancer. This Milestone:

• Explores the first identified mechanisms of resistance to targeted treatments.
• Reports on the first trial to show that a bivalent vaccine for HPVs 16 and 18 could reduce cervical cancer risk.
• Highlights the papers that reported that defects in BRCA1 or BRCA2 are synthetically lethal with loss of PARP function.
• Explores the first whole-genome sequence of a cancer.
• Reports on the first papers to show mutations in histones in paediatric high-grade gliomas.
• Describes the landmark discovery that the gut microbiome is a modulator of response to cancer therapies.

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Nature Portfolio is pleased to acknowledge financial support from Illumina, Inc, Johnson & Johnson and grant support from AstraZeneca, Boehringer Ingelheim International GmbH, and Merck & Co., Inc., Kenilworth, NJ, USA  in producing this Nature Milestone.