In October 2019, the AACR, NCI and EORTC held their joint International Conference on Molecular Targets and Cancer Therapeutics in Boston, MA, USA. This annual event, which has been held for 30 years, provides a key opportunity to keep abreast of the busy field of translational oncology, and this year’s programme did not disappoint.

The conference started with an insightful educational session in which Jaap Verweij, Elizabeth Fox and Michael Heinrich reflected on the successes and failures of targeted therapies over the past 20 years. Despite covering different cancer types, the presenters agreed on the need for appropriate preclinical models and the importance of joining resources for conducting clinical trials.

Both a keynote lecture and a dedicated session focused on targeted protein degradation with agents exploiting the cereblon–E3 ligase interaction as well as proteolysis-targeting chimeras (PROTACs). The studies presented addressed the biochemical principles guiding interactions that result in the degradation of oncogenic proteins. This knowledge has been gained from decades of study of the mode of action of lenalidomide. Major excitement surrounds these therapeutic approaches; however, their incorporation in clinical studies remains limited.

In ‘spotlight’ sessions, the authors of ten submitted abstracts were given the opportunity to present the results of ongoing early phase clinical trials. The agents tested in these studies are targeted at a variety of biological processes that are dysregulated in cancer, such as DNA repair, RNA splicing, interactions with immune cells or oncogenic RAS signalling. Great excitement surrounds the latter target, with recent advances in this area also being discussed in a dedicated session.

Not surprisingly, targeting DNA repair was a common theme in many presentations. The success of this therapeutic approach typically depends on exploiting cancer-specific dependencies, such as synthetic lethality, genome instability or oncogene-induced replication stress.

Bissan Al-Lazikani, Adam Dicker and Sean Khozin provided a comprehensive view of how preclinical and clinical data can be integrated to provide optimal patient-centred care. Practical examples include designing tailored treatments, evaluating treatment-related quality of life or identifying patterns of response to treatment in large patient populations.

The variety of topics covered is one of the strengths of this year’s programme; important areas that cannot be summarized herein include immuno-oncology and liquid biopsies. In summary, the complex network of mechanisms that are dysregulated in cancer cells and their environment was highlighted at the conference. The good news is that joint research efforts are enabling the development of approaches to target these mechanisms, some with promising results in early phase trials. We look forward to next year’s meeting in Barcelona, at which additional novel targeted therapies are likely to be presented.