cancer metabolism Archives - Sanford Burnham Prebys
Institute News

Preeminent scientists present at SBP’s Cancer Metabolism Symposium

AuthorSusan Gammon
Date

June 27, 2018

SBP’s 4th Cancer Metabolism Symposium attracted nearly 150 attendees—all eager to learn more about how the nation’s top-tier cancer scientists are looking to target tumor metabolism.

Research on cancer metabolism is critical to identify new therapeutic targets to starve tumors of the fuels and building blocks they need to grow. Recognition and understanding of the impact of cancer metabolism will increasingly and positively affect the development of novel anti-cancer therapeutics.

The event featured 21 speakers who presented the latest concepts and models in the field of tumor metabolism, which expands to other areas of cancer biology, including microenvironment, immunometabolism and cell bioenergetics. All of the presentations addressed fundamental mechanisms of cancer as well as how this emerging field of science is impacting translational research and personalized medicine. 

“It’s an honor to host the top experts in the field and discuss what we know about metabolic wiring in tumors and their environment,” said Jorge Moscat, PhD, conference co-organizer and director and professor of the Cancer Metabolism and Signaling Networks Program at SBP. “These events will lead us to strategies to exploit tumor vulnerabilities and better ways to treat cancer.”

Keynote speaker M. Celeste Simon, PhD, who studies cancer metabolism and the influence of oxygen availability on tumor growth, presented her recent data on “Metabolic Symbiosis in the Hypoxic Tumor Microenvironment.” Simon, a recipient of a National Cancer Institute Outstanding Investigator Award, is a leader in biomedical research on cancer metabolism, specifically renal cancer, which is one of the 10 most common cancers in both men and women. She is scientific director of the Abramson Family Cancer Research Institute of the Perelman School of Medicine at the University of Pennsylvania.

“These conferences are important because they give scientists an opportunity to share new ideas and promote collaborations that can enhance accelerated discovery and development of new therapeutic approaches to target cancer metabolism,” says conference co-organizer Maria Diaz-Meco, PhD, professor in the Cancer Metabolism and Signaling Networks Program at SBP.

Robert Abraham, PhD, Pfizer Worldwide Research & Development, represented the industry side of research with a presentation titled “Probing Cancer Metabolism with Cancer Drugs.”

Academic biomedical research institute speakers were represented by the Symposium’s organizers, Moscat and Diaz-Meco; and a broad range of acknowledged leaders in cancer research, including Ronald DePinho, MD (MD Anderson Cancer Center); Ramon Parsons, MD, PhD (Mount Sinai); John Blenis, PhD (Weill Cornell Medicine); Reuben Shaw, PhD (Salk Institute); Eileen White, PhD (Rutgers Cancer Institute of New Jersey); Tak Wah Mak, PhD (University of Toronto and The Campbell Family); Alec Kimmelman, MD, PhD (NYU Langone Health); Karen Vousden, PhD (The Crick Institute); Ralph J. DeBerardinis, MD, PhD (University of Texas SW Medical Center); Roberto Zoncu, PhD (UC Berkeley); Christian Metallo, PhD (UC San Diego); Douglas Green, PhD (St. Jude Children’s Research Hospital; Matthew Vander Heiden, MD, PhD (David H. Koch Institute at MIT); Dafna Bar-Sagi, PhD (NYU Langone Health); Michael Karin, PhD (UC San Diego); Jeffrey Rathmell, PhD (Vanderbilt University); and Davide Ruggero, PhD (UC San Francisco).

“We wish to thank all the speakers, attendees and support staff that helped pull this amazing conference together,” said Moscat. “We look forward to planning SBP’s next cancer metabolism conference to continue sharing breakthrough research advances that will ultimately improve the lives of patients.”

Institute News

Research points to possible target to stop cancer stem cells

AuthorJessica Moore
Date

July 28, 2016

When you think of stem cells, you probably think of healing and regeneration—cells that can replace tissue lost to disease or injury. But tumors also arise from stem cells—a specific kind called cancer stem cells. Because these cells can divide indefinitely, while other cancer cells’ proliferation is more limited, therapies that get rid of them would eventually stop a tumor from growing, and from ever coming back.

Researchers in the laboratory of Dieter Wolf, MD, professor in the NCI-Designated Cancer Center, may have found a new way to do this, though in a roundabout way. While examining the function of two proteins found at high levels in tumors, they discovered that these factors are required for a type of metabolism that’s essential for cancer stem cells to survive.

“Our findings suggest that these components, eukaryotic initiation factors (eIFs) 3d and 3e, are novel targets for eliminating cancer stem cells,” said Wolf, senior author of the study, which was published in Cell Reports. “If we could find a way to turn these factors off, we could starve cancer stem cells.”

The details

eIF3d and eIF3e are part of the complex that initiates protein synthesis, also called translation. Specifically, they and other eIFs help bring the ribosome, which builds proteins by linking amino acids one by one, to messenger RNA, the molecules that carry the code the ribosome reads, specifying which amino acid should be added next.

Wolf’s team was interested in whether overproduction of eIF3d and eIF3e promotes cancer progression. To determine their function, they compared the amounts of all proteins made in cells lacking these factors to those in normal cells. A difference that stood out was in the levels of the protein complexes required to produce ATP, the cell’s energy currency, in mitochondria—eIF3d/e-deficient cells produced far lower amounts than normal.

“Cancer stem cells, unlike most tumor cells, rely on mitochondrial metabolism for energy,” Wolf explained. “Since tumor cells have much higher levels of eIF3d/e than normal cells, inhibiting those factors would preferentially block metabolism in cancer stem cells.

“Our results are somewhat surprising because eIF3 has long been thought to control the synthesis of all proteins. Instead, our data suggest that some parts of eIF3 selectively recruit certain mRNAs.”

Next steps

“We’re now examining how eIF3d/e affects cancer metabolism overall to see if these factors might be relevant to more than just cancer stem cells,” added Wolf. “Also, as a step towards advancing this research to the clinic, we’re designing screens to identify small molecule inhibitors of eIF3d/e.”

The paper is available online here.

Institute News

Cancer metabolism symposium highlights hot area in cancer research

AuthorJessica Moore
Date

June 27, 2016

The third Cancer Metabolism Symposium held at Sanford Burnham Prebys Medical Discovery Institute (SBP) June 22-23, 2016, attracted a full house of attendees from across San Diego. Its success likely results from the impressive roster of speakers invited by organizers Jorge Moscat, PhD, professor and director of the Cancer Metabolism and Signaling Networks Program, and Maria Diaz-Meco, PhD, also a professor in that program. The presenters included numerous thought leaders in the field from such prestigious institutions as the Koch Institute for Integrative Cancer Research at MIT, the Dana Farber Cancer Institute at Harvard Medical School, and Memorial Sloan Kettering Cancer Center.

The aim of research on cancer metabolism is simple—to find ways to starve tumors of the fuels and building blocks they need to grow. This strategy is gaining attention (see this recent New York Times feature) because of the increasing evidence that cancer cells obtain and use nutrients differently than normal cells. Plus, there appear to be a few common ways in which cancer cells’ metabolism becomes deranged, making it a much simpler target than oncogenic mutations, which tumor cells accumulate almost exponentially.

Several new drugs that interfere with metabolism have shown promise in clinical trials for numerous types of cancer. Nonetheless, there’s still a lot to learn. Since tumor cells rely on the same metabolic pathways as normal cells, researchers must pinpoint cancer’s weaknesses—the enzymes and nutrients on which cancer cells rely far more than normal cells. Many of these differences were discussed at the symposium, opening doors for new ways to stop cancer.

Institute News

SBP presents at American Association for Cancer Research’s annual meeting

AuthorKristen Cusato
Date

May 10, 2016

Deputy Director of the NCI-designated Cancer Center, Jorge Moscat, PhD, and Cosimo Commisso, PhD, assistant professor in the Center, presented at the AACR conference in New Orleans.

Moscat presented at the session titled “Metabolic Interplay between Tumor and Microenvironment.”

“Cancer cells have to adapt their metabolism to survive nutrient deprivation and several stress conditions in their tumor microenvironment. For this they put in motion a process called autophagy whereby they get rid of toxic intracellular molecules and organelles and generate nutrients that allow them to survive,” said Moscat.

“Central to this process is a protein called p62 that was discovered in collaboration with my SBP colleague Maria Diaz-Meco. This protein is upregulated in, for example, liver cancer, whose mortality has increased dramatically over the last 10 years, in marked contrast to many other neoplasias that have shown a significant decrease in mortality.

“We presented new compelling data from human patients, mouse models and cell culture studies demonstrating that inactivation of p62 in cancer liver cells dramatically reduced the incidence and aggressiveness of hepatocellular carcinoma. Therefore, p62 is a novel and potentially actionable therapeutic target in liver cancer,” added Moscat.

Moscat said he was impressed at AACR by the number and quality of research studies linking the possibility of treating patients by a combined strategy of targeting cancer metabolism and the immunological tumor microenvironment.

He also spoke to ecancer.tv, an online provider of oncology news, about his research. Watch the video here.

Moscat is co-chair of a symposium on related research in cancer metabolism to that will be held June 22-23 at SBP’s La Jolla campus.

Commisso’s presentation was featured in a special session on pancreatic cancer that aimed to stimulate opportunities for collaboration between Pancreatic Cancer Action Network-AACR grantees and others in the field.

“The research that I presented was focused on a novel drug target in pancreatic cancer discovered recently by my lab,” said Commisso.

“We have found that an ion transporter that regulates pH homeostasis is critical to pancreatic cancer cell survival. This previously uncharacterized transporter plays a role in maintaining amino acid supply in tumor cells that harbor a mutation in the oncogene known as Ras, which is mutated in >90% of pancreatic tumors.

“Our future work is focused on exploring the role of this transporter in preclinical models and developing new approaches to inhibit this druggable target,” added Commisso.

He called the AACR meeting “a remarkable opportunity for cancer researchers to come together and share their exciting discoveries.”  Dr. Commisso also said it was a good opportunity to connect with colleagues and friends to develop and nurture scientific collaborations, to create, progress and build.

Commisso will also present at the 2016 PancWest Symposium in September at the Moores Cancer Center at UCSD.

Institute News

Cancer metabolism 101

Authorsgammon
Date

April 21, 2015

 

“Feed me!” Cancer is caused by the uncontrolled proliferation of cells. Their rapid growth comes with a voracious appetite to support their nutritional demands. To satisfy these demands, cancer cells rewire their metabolism. Increasingly, scientists are looking to exploit the metabolic differences between normal and cancer cells for the development of new anti-cancer therapies. Continue reading “Cancer metabolism 101”