In Focus social interactomes for enabling Research Communities

interactome Social interactome Presentation of survey results at the conference and small group discussion Research. on November 28, 2014. © 2014 American Association for Cancer cancerdiscovery.aacrjournals. org Downloaded from November 2014 CANCER DISCOVERY | 1267 views question surveys, reflecting the enthusiasm of the RAS community and the willingness of researchers to be engaged on their primary research topic. A key objective of the survey was to identify popular and interesting areas of research within the RAS community. Exciting developments reported by 2013 AACR Annual Meeting attendees involved resistance mechanisms to EGFR/ BRAF inhibitors, the role of wild-type RAS isoforms in KRASdriven tumors, and the intriguing dependency of KRASmutant models on activation for enhanced activity. In 2014, areas with promising achievements changed considerably as compared with previous years, with major interest in drug design for direct or indirect RAS targeting, preclinical– clinical translation with novel agents and combinations of targeted therapies in RAS/RAF–driven models, the role of oncogenic KRAS in metabolic reprogramming, and its interaction with the tumor microenvironment. Top publications in the field repeatedly mentioned by respondents reported the development of compounds that bind to well-defined surface pockets on oncogenic KRAS in a mutant-specific manner (2, 3) or that inhibit its interaction with plasma membrane/ scaffold proteins (4, 5). In line with these findings, in 2013, the most pressing question for RAS scientists concerned the druggability of KRAS, whereas in 2014, investigators were mainly interested in preclinical–clinical translation of KRASinteracting agents. We also asked attendees to revisit previous work in the RAS–RAF–MAPK domain and give an impartial opinion on areas of research that they consider oversaturated with repetitive findings or with results that are not reproducible. Many groups reported the failure to validate potential targets described in the literature as synthetic lethals in KRAS-mutant models as the major unexpected finding. Apart from high-throughput RNA interference screen studies, publications that attracted less attention from respondents in 2014 as compared with 2013 included those evaluating the preclinical activity of MEK inhibitors in combination with PI3K pathway inhibitors in KRAS-mutant models, resistance to selective BRAF inhibitors in melanoma, and genomesequencing studies assessing the molecular epidemiology of RAS/RAF. On the other hand, recurring topics with the highest interest for future research and that need more investment according to attendees were predominantly preclinical experiments linked to drug design and functional and systems biology approaches for studying MAPK pathway regulation in RAS-driven tumors. Most importantly, this exercise set the scene for the second part of the RAS interactome sessions, when we organized small group discussions, allowing similarly minded researchers to interact face to face. In these breakout sessions, tables of 10 to 15 people were set up, with placards at each table describing a subtopic within the RAS community, including “models of RAS,” “RAS regulators,” “metabolism,” “microenvironment,” “RAS drug targeting,” “preclinical–clinical translation,” and “clinical validation. ” Attendees were asked to share their research questions and problems and to find areas where topic discussions and/or future collaborations could help resolve existing research bottlenecks. To understand the benefit of this breakout session, we sent out a follow-up survey after the conclusion of the 2014 AACR Annual Meeting. We received close to 50 responses, all of them reporting positively on the session and 11 describing new collaborations as a direct result of the breakout discussions. A common request was for greater structure within the discussion sections, with predefined leaders and more specialized topics of discussion. These comments reflected our own underappreciation of the desire for structured, albeit informal, discussions among conference attendees, and will be emphasized at future interactome sessions. FuTuRe oF BIomeDIcaL conFeRences The large attendance, enthusiastic response, and active participation by those at these AACR special sessions demonstrate a desire for alternative forms of interactions at biomedical conferences. Indeed, the need for roundtable dialogues engaging fellow scientists is a clear message of these experiments and should compel AACR and other organizations to expand this type of meeting to other areas. We therefore recommend the following components as important areas of attention for future conference planning.