The 12^th Annual Forbeck Scholar Retreat was held over a rainy but mild weekend at the very attractive Geneva National Resort.  The meeting brought together Scholars who were selected from the Resistance Mechanisms (2013), Invasion and Metastasis (2014), Immunotherapy (2015), and Chromosomal Aneuploidy (2016) Forbeck Forums.  The overall goals of the Scholar Retreats are to stimulate cross-disciplinary discussion between researchers, to provide mentorship on career development from senior scientists, and to create camaraderie among the group leading to long-term friendships and research collaborations. These goals are facilitated by unique structure of the Forbeck meetings.  The participants kept with the spirit of the 5-slide format, which stimulated lively and sometimes heated discussion. Debates and exchange of ideas continued into breaks and meal times. Interactions with Foundation members and donors, as well as patient and their families at the social events provided further inspiration for the group.  

The meeting was kicked off by a keynote address from Dr. Raul Mostoslavsky, Associate Professor of Medicine, at Massachusetts General Hospital Cancer Center and Harvard Medical School. He spoke about his journey as a scientist from being a medical student in a provincial town in Argentina to studies across 3 continents leading to his establishment of his own laboratory in Boston. He stressed the serendipity of discovery and the values of open-mindedness, curiosity, and collaboration. Emphasizing the privilege of being able to do scientific research, he motivated us all.  

The scientific sessions began with Kris Sarosiek, Corey Johannssen, and Kris Wood speaking on Drug Resistance. In the last 15 years, there have been considerable advances in developing treatments that are specifically tailored to subset of patients depending on the genetic features of their tumors. While such therapies are often initially effective, they are rarely curative. Recurrence usually happens rapidly due to acquired mutations that render the original drug ineffective. The speakers each described sophisticated new technologies addressing a range of related topics including finding ways to prevent drug resistance by more effectively choosing the right drug for a given patient, understanding the strategies used by cancer cells acquire resistance, and discovering drug combinations that revert resistant cells into being sensitive. While this will unfortunately be the final Forbeck meeting for this group of graduating Scholars, their success is a testament to both their abilities and the value of the Scholars program. Each of them is now an independent faculty member running his own laboratory, and they have effectively collaborated with other scholars in published papers and team grants over the last few years. The Drug Resistant Scholars nicely anticipated the talk by Mentor Marion Dorsch.  She outlined the power of chemical biological approaches in development precise molecular medicines, and discussed the puzzle of predicting which patient is most likely to respond to a given drug.  The very fruitful discussions of the group with Marion highlighted the essential synergy of academia-industry partnership in advancing cancer science and patient care.  

Mentor, Steve Artandi, presented a fascinating discovery that rare cells in the liver have a different biological function than their otherwise similar neighbors in this tissue—The work has very important implications for how liver cancers originate and how the liver repairs itself following injury.  The next set of talks related to Metastasis, presented by Chad Pecot, Mario Shields, and Louise Van der Weiden.  They discussed the use of powerful genetic approaches and sophisticated microscopy to study different mechanisms for how cancer cells leave their original site and invade other tissues, which is the main cause of death for most cancer types. Their studies examined the dissemination of cancer cells through either the blood or lymphatic system, and assessed how changes in connective tissue and immune cells can regulate the ability of a cancer to metastasize.  Next came the Immunology Scholars, Esra Akbay and Annette Kunkele.  Cancer Immunology is one of the most rapidly advancing areas in current oncology and seeks to promote the ability of the immune system to recognize the cancer cells as foreign invaders and to kill them off just as the immune system kills pathogens.  However, many cancer types have evolved to evade the attack of the immune system, through a variety of mechanisms that are only partly understood. The Scholars spoke the ability of certain gene mutations in the cancer cells to turn off the immune response or to make the tumor cells invisible to the immune system as well as about strategies to reinvigorate the immune system to recognize and kill off cancer cells.  

The aneuploidy Scholars Uri Ben-David, Lilian Kabeche, Stefano Santaguida, Neil Umbreit, and Jason Sheltzer spoke next.  Aneuploidy refers to abnormalities in whole chromosomes or large parts of chromosomes.  While aneuploidy is a well-known characteristic of most cancers, it remains uncertain to what extent aneuploidy causes abnormal cell growth nor how cell cope with abnormal numbers of chromosomes.  The talks addressed the use of ‘big data’ to uncover vulnerabilities of cancer cells with aneuploidy and to establish which genomic features of a tumor predict whether it will have an aggressive clinical course.  Other talks revealed a new role for immune cells in detecting and killing aneuploid cells. Finally, work was presented on how aneuploidy arises in an otherwise normal cell. These studies make predictions about how cancers initial develop and about novel treatment strategies.  

Mentor Katie Wellen spoke about how cancer cells use nutrients such as sugar (glucose) for a variety of purposes including regulating the packaging of genes into complex structures referred to as chromatin.  This provides a whole new window into how the acquisition and utilization of essential fuels can be diverted for the growth of a cancer. Katie was a former Scholar (class of 2012) who is now a very successful faculty member at University of Pennsylvania. Mentor Raul Mostoslavsky spoke about a related topic of how the SIRT6 protein normally playing roles of sensing nutrients is also essential for preventing the aggressive and metastatic growth of pancreatic cancer.  Finally, meeting Chair, Nabeel Bardeesy (former Scholar, class of 2004) provided an overview of a biochemical pathway involving the GNAS protein that is normally required for the response of tissues such as the liver and fat cells to hormones that change metabolic function. He discussed how gene mutations in this pathway lead to cancer growth.  

The Scholars and Mentors then retired to the cabins for a Q & A session regarding career development challenges. Great fun was then had at the Blue Jean Ball, with Lauren and the extended Forbeck Family and friends. It was a very rewarding evening, with both friendship and serious discussion. It was a treat to speak with members of the public about cancer research and it was very moving to hear about their experiences and concerns regarding the effects of cancer on their lives. Nevertheless, the wine tasting made sure the mood stayed light, and brought people together further.

I wish to thank the Mentors who took their time to attend the meeting and help guide these promising Scholars as their career is at its most crucial time. Those mentors who had not previously been to a Forbeck event found that the Retreat was a revelation in how scientific communication should work, and were in great admiration for the commitment of the Foundation to create and maintain such great legacy of contribution to the cancer research community.  Finally, and most importantly, I thank John, Jamie, and Lauren, and all the volunteers and supporters of the foundation for making this event happen.  The Foundation plays a truly unique role in the cancer research world, and it is extraordinary that its contributions remain as fresh and important as ever.  I am very grateful to have had the opportunity to participate in this recent meeting and to continue to serve on the SAB.

Top 3 Take Aways

1. The meeting brought together Scholars from areas of research in Resistance Mechanisms, Invasion and Metastasis, Immunotherapy and Chromosomal Aneuploidy.  The overall goals of the Scholar Retreats are to stimulate cross-disciplinary discussion between researchers, to provide mentorship on career development from senior scientists, and to create camaraderie among the group leading to research collaborations.

2. The meeting was kicked off by a keynote address from Dr. Raul Mostoslavsky, Associate Professor of Medicine, at Massachusetts General Hospital Cancer Center and Harvard Medical School. He spoke about his journey as a scientist from being a medical student in a provincial town in Argentina to studies across 3 continents leading to his establishment of his own laboratory in Boston. He stressed the serendipity of discovery and the values of open-mindedness, curiosity, and collaboration. Emphasizing the privilege of being able to do scientific research.  He motivated all who attended.  

3. Those mentors (senior scientists who had not previously been to a Forbeck event) found that the Retreat was a revelation in how scientific communication should work, and were in great admiration for the commitment of the Foundation to create and maintain such a great legacy of contribution to the cancer research community.  The Foundation plays a truly unique role in the cancer research world, and it is extraordinary that its contributions remain as fresh and important as ever.

‍