Hamilton fairley award

ABSTRACT In the last 5 years, there has been a major acceleration of the understanding of the molecular alterations responsible for cancer cells development. Large variety of genomic and epigenetic alterations, resulting in abnormal gene expression patterns, and cellular behavior can now be uncovered for each individual tumor. New nosological classifications, across and within histological subtypes, are emerging as a consequence of this knowledge resulting in a fragmentations of previous disease types mainly organ-based in a myriad of rare tumors. This complexity is multidimensional, and only starts to be understood, with the additional challenge that it evolves over time within subclones of tumor cells in each individual patients. Despite these challenges, the partial understanding of this complexity we have reached has led to tremendous progresses for the treatment of patients with cancer recently, e.g. in CML, HER2+ breast cancer, GIST BRAF mutated melanomas, Alk mutated tumors. In each example, the targeting of a “key node”, a driver alteration in the process of neoplastic transformation, or tumor progression was often sufficient to achieve a major improvement. The identification of these driver mutations has sometimes been stochastic, emerging from translational research programs aiming to find predictive factors, but is now more often coming from a rationale systematic approach to identify subgroups of cancers with similar genomic alterations. Novel nosological classifications must be built with these tools, and our treatment paradigms will be based on these. However, obvious obstacles are already visible: clonal heterogeneity of cancer, frequent emergence of resistance, integration of treatment targeting the immune stroma, but also compliance for long term treatment, and economical considerations. In this presentation, we will show some successful and non successful examples of development of targeted treatment to which we have contributed, and the lessons which should be drawn from these examples for the future development of anticancer therapies. Disclosure The author has declared no conflicts of interest.