Cancer remains a major cause of mortality worldwide, and despite the large amount of efforts and money invested in its understanding and treatment together with the large therapeutic arsenal available, complete responses are rare, and partial responses are limited in duration. Until recently, cancer pathogenesis and evolution was “equivocally” well-understood by both physicians and researchers as a clonal entity with a lineal evolution in which temporal accumulation of genetic instability was a hallmark. As a consequence, many academic and industry therapeutic efforts focus on killing the bulk tumor and, hopefully, the cancer-initiating cells responsible for fueling the tumor growth and underlying long-term relapses. However, recent cutting-edge advances in next-generation sequencing, bioinformatics and xenograft models have revealed an unprecedented and “scary” view of the cancer genome and its evolution.

Thanks to innovative cancer researchers and geneticists together with evolutionary biologists and computational biologists, it is nowadays well-accepted that cancer responds to an evolutionary process whereby, cancer affecting different tissues and ages evolves by a reiterative stepwise process of clonal expansion, genetic diversification and clonal selection within the adaptive landscapes of tissue ecosystems. The highly variable and dynamic patterns of genetic diversity results in a complex intratumor heterogeneity (ITH), suggestive of a branching clonal architecture for any tumor. Therapeutic intervention may destroy specific cancer clones while is likely to inadvertently provide a robust selective pressure for the expansion of other clones with a distinct genetic composite. Thus, this emerging complexity in intraclonal cancer evolution has been attributed to Darwinian evolutionary principles which may underlie the therapeutic failure through the ability of specific clones, even the ones carrying the oncogenic initiating event, to become refractory to therapy.

ITH and clonal evolution is expected to have a huge impact in cancer biology. Despite it still needs to be addressed, the clinical significance of ITH and its evolution and dynamics over time in response to cancer therapies is anticipated to become of upmost relevance for the way we diagnose, treat and follow-up cancer patients. Emerging questions are: i) Will we ever manage to achieve long-term complete responses using targeted monotherapies; or polytherapy will be necessary to cope with ITH-mediated malignancy? ii) Does it become crucial to identify the bona fide initiating/driver oncogenic event to develop therapeutic strategies targeting such an insult? iii) would cancer patient stratification at the time of diagnosis need to be revisited? iv) Should we apply this emerging knowledge to the way we measure minimal residual disease in follow-up studies?. The necessary tools are now available to prospectively determine whether clonal heterogeneity can be used as a biomarker of clinical outcome.

In this ICREA-FIJC conference we will discuss how studies relying on longitudinal tissue sampling, integrating both genomic and clinical data, may assist in the clinical practice by defining the breadth of genetic diversity in different tumor types, and its relevance to treatment failure, molecular follow-up, and eventually patient outcome.  During two days, outstanding researchers and physicians will come together to revise current challenges in cancer treatment and therapy resistance and to discuss about future strategies and tools to dissect ITH at basic and clinical level.

The organizing committee is looking forward to welcoming you to this fascinating meeting in the stunning, multicultural and modern city of Barcelona. Hope to see you there to welcome the spring!

The Organizing Committee