A defining feature for many cancer types is their ability to rapidly evolve, making them a hard-to-treat moving target. This meeting will bring together experimental, computational, and clinical cancer researchers, in an attempt to find unifying principles of cancer evolution and to identify related targetable vulnerabilities. The main theme of this meeting will be to explore mechanisms of cancer evolution at different scales: from somatic mutations and long-term clonal evolution to chromosome instability and chromosome-level catastrophes that lead to acute evolutionary bursts and tumor population heterogeneity. The meeting will consist of four sessions, each focusing on a different genomic scale:

Session 1: From letters to genes (bp-kb scale)
The contribution of DNA damage, mutations, and cancer relate genes (oncogenes/TSGs) to cancer evolution

Session 2: Sub-chromosomal structures (kb-mb scale)
The contribution of unique sub-chromosome structures (centromeres, telomeres, ecDNAs, HSRs) to cancer evolution

Session 3: From chromosomes to genomes (mb-gb scale)
The contribution of chromosome instability, aneuploidy, and whole genome doubling to cancer evolution

Session 4: Cells, populations, and beyond (>gb scale)
The impact of cancer genome evolution on the tumor microenvironment, metastasis, and therapy resistance

Each of the sessions will address the following topics:

1. How to study cancer evolution: Revisiting the tools used to study cancer evolution
2. What have we learned about cancer evolution: Characterizing pan-cancer principles of cancer evolution
3. What are the clinical implications of cancer evolution: Exploring the role of cancer evolution in therapy resistance formation
4. Actionable items for improved therapy design: Identifying approaches targeting the evolvability of cancers

This meeting will provide a unique opportunity to bring together scientists and physicians from different fields of cancer research. Each expert will provide a distinct point of view that together could have the potential to synthesize into new ideas that lead to paradigm shifts. The connections formed between participants will foster new collaborative efforts, thereby realizing the spirit of the Forbeck Foundation.

RELEVANCY

Recent efforts revealed the magnitude of genome complexity in cancer and allowed delineating trajectories of cancer evolution. As new therapies are being introduced in the clinic, it becomes clear that resistance poses a critical challenge, but how cancers evolve to become resistant to different therapies is a matter of active research. The advent of new methodologies such as CRISPR-Cas9, long-read DNA sequencing, and single-cell assays now provide the opportunity to gain unprecedented resolution on the underlying mechanisms of cancer evolution and therapy resistance. This meeting will serve as a platform that joins mechanistic experimental biology and powerful computational analyses, with emerging clinical challenges, to provide novel insight in on cancer evolution and its implications for therapy design.

GOALS

In this meeting we aim to achieve the following goals:

1. Bringing together experimental, computational, and clinical cancer researchers, that ordinarily do not get the chance to meet. This will hopefully encourage participants to share more unpublished data and lead to more holistic discussions during the meeting.
2. Crystalize new thoughts and ideas thus providing new avenues of research with clinical prospect. Each invited participant is an expert on a different cancer type or uses a unique scientific approach. The collection of participants will hopefully synergize to create new and exciting science.
3. Formation of new collaborative efforts. The selection of participants was made such that there will be minimal overlap and competition, and a high degree of complementation and shared scientific interest. This will hopefully lead to new collaborations.

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