In Summary (very briefly) how would you explain what was covered in this forum. Simplest terms.
The past meeting, held in Denver from October 17-19, was the second Forbeck meeting on telomere biology. Since the last meeting, 17 years ago, great progress has been made in the field and several cancer-relevant aspects of telomere biology as it relates to cancer were discussed vigorously. Relevant to neuroblastoma, a recent meeting in the UK addressing new drug development strategies for this disease as well as a recent publication, reported that patients with high telomerase activity have overall poorer outcomes. We had a detailed discussion on how to target telomerase in cancer, exploring the pros and cons of telomerase inhibitors and so-called telomerase poisons, one of which has already been shown to be effective in neuroblastoma cell lines. We also discussed the potential deleterious consequences of telomerase inhibition based on new clinical knowledge of inherited telomere diseases which mimic telomerase insufficiency.

Several clinicians discussed the challenges of treating such patients as well as the implications of patient data for understanding the role of telomeres in cancer. An important aspect of our discussion focused on recent new findings that indicate that children born with overly long telomeres are predisposed to cancer. In addition, we discussed the mechanisms by which loss of telomeres drive changes in the cancer genomes and the potential of gleaning actionable information from the current NextGen cancer genome sequencing efforts. Finally, a considerable part of our discussion was focused on a second pathway for telomere maintenance, called ALT. The ALT pathway is highly significant to neuroblastoma since a substantial number of patients have cancers that employ this pathway. This pathway has been known for a long time but was poorly understood. Recent progress now has revealed the details of how ALT works and is beginning to suggest how ALT could be targeted in the cancer clinic.

Why was this meeting relevant now?
As humans age, the ends of linear chromosomes, telomeres, become progressively shorter. Short telomeres elicit a DNA damage response and can induce either senescence or apoptosis both of which can halt tumorigenesis. Telomerase, the enzyme that elongates telomeres, can counteract telomeres shortening and prevent senescence and apoptosis. This enzyme is absent from most normal tissue but is often activated in cancer. Recently it has become clear that telomerase activation is a highly selected aspect of tumorigenesis, often occurring through point mutations in the promoter of the gene encoding the limiting component of telomerase. While telomerase is not oncogenic per se, it is almost universally required to permit the indefinite growth that occurs as part of cancer progression. The recent data on mutational telomerase activation has confirmed the view that telomerase is a required aspect of cancer cell proliferation and further supports the view that inhibition of telomerase should be an effective cancer therapeutic. These and other new data on telomeres and the role of telomeres in cancer made the discussion in the context of the Forbeck forum highly appropriate and timely.

The meeting was viewed as highly successful by all participants and several new collaborations were initiated at the meeting. The Forbeck scholars were all excellent and participated throughout the meeting in a very productive manner.

What came out of this meeting? Conceptual, collaborations any papers or experiments.
It was almost universally mentioned that this was one of the best meetings most participants had attended in a long time. The format of not having a lot of data slides but having discussions was very successful. A number of discussions about collaborations going forward were also initiated.

What do you see developing in this field from this meeting?

1. Better approaches for treating patients with genetic disorders of telomere maintenance
2. New approaches to targeting telomerase and ALT cancers
3. A better understanding of which cancers are the best candidates for telomere-based therapies

How does this impact patients today?
Several approaches to leverage the biology of telomeres are currently in clinical development so optimism is high that in the near future new approaches to treating patients with cancer will occur.

‍