The Forbeck Forum on Targeting Lipid Biology in Cancer took place in the picturesque Asilomar conference center in Pacific Grove, California which included biologists, chemists, and physician scientists working broadly in the fields of lipid signaling and metabolism to help develop strategies to better target lipid pathways and improve our understanding how these pathways are dysregulated in cancer. The Forum was divided into 4 sessions, structured to (1) Lipid signaling and trafficking in cancer; (2) Lipid metabolism in cancer; (3) New lipid tech applications in cancer; (4) Drug development and clinical trial design.  From these

4 sessions some major themes arose which were actively discussed throughout the meeting.  

There are many unsolved mysteries on the role of lipids in cancer:
Although it is clear lipids control tumor growth, cancer scientists today do not understand how oncoproteins that produce those lipids are turned on and off. There are almost certainly opportunities to develop better cancer drugs if we had a clearer picture of how those oncoproteins are regulated to control the levels of lipids in tumors. Along those lines, many oncogenes that control lipid abundance in tumors are overexpressed in cancers, but it is unknown what specific role these genes play in tumor biology, or the details of how the lipids control the growth and survival of tumors. We need better chemical tools to understand how these genes stimulate tumor growth. It’s also becoming clear that age impacts the tumor microenvironment and the lipids within the microenvironment affect tumor growth, however the details of how a patient's age stimulates tumor growth remain almost a complete mystery.

Basic connections between lipids and cancer need clarification:
At this meeting, there was consensus that the lipid cancer research community needs improved molecular markers for a membrane structure called the "endosome", so that scientists can better characterize how particular oncogenes and tumor-suppressor genes cause cancer. Cancer-relevant lipids have also recently been discovered to co-localize with atypical structures in tumor cells. Although these structures are established to be required for faithful growth of normal cells, it is unclear how disruption of the lipids at these sites causes cancer, or stimulate tumor survival/growth. It is clear that very common metabolites which are present in both healthy and tumor tissues participate in regulating important tumor proteins that remodel membrane lipids to become oncogenic, however it is unknown how these proteins "sense" those metabolites. Advances in these areas could significantly impact how lipids control tumor growth.

Which lipid-based cancer targets should we pursue for new drugs?
Another theme that emerged was that there are some cancers, often ultra-rare cancers, that universities might be better suited to pursue in drug design efforts, as opposed to large pharmaceutical companies. One such tumor may be adrenocortical cancer. Further, drugs directed against the PI5P4K lipid enzymes have high therapeutic potential in several cancers, including breast and pancreatic cancer.  There was also agreement that the presence of pharmaceutical industry professionals at Forbeck Forums may facilitate more effective anti-cancer drug development efforts.

‍New and druggable cancer targets:
Using technology available today, basic scientists can decrease the number of "mutations of unknown significance" and increase the confidence in predicting if a tumor is benign or aggressive.  PI5P4K has high therapeutic potential in several cancers, including pancreatic cancer.  NR5A1 appears to be an excellent target in adrenocortical cancer.  Despite recent setbacks, PI3K delta inhibitors could be clinically useful in combination or if administered to the appropriate patient population.  

New tools to help surgeons and scientists:
Innovative surgical tools that allow surgeons to monitor the lipid content of resected tumor tissue in seconds, within the operating theater, permit cleaner margins and better outcomes for patients. Tumor imaging provides data that is rich with information about the tumor, but we as scientists are not taking full advantage of all the data collected from tumors because we tend to use simple analyses. We need to take advantage of time-resolved imaging to unlock higher quality diagnostic and biomarkers for clinical trials.

In summary, this forum inspired brilliant discussions and interactions among participants from diverse backgrounds, ultimately fueling several new collaborations which will result in impactful papers, grants and importantly better clinical trial design strategies.

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