ASCB Opens the Door to the New Cell Biology of Cancer

alan ashworth

Alan Ashworth, President of the UCSF Helen Diller Family Comprehensive Cancer Center, is a co-organizer of the Cell Biology of Cancer meeting.

A doorstep meeting is an arrival and a departure in one, so the name suits the ASCB’s first-ever “doorstep” meeting on the Cell Biology of Cancer. It will be both. The Cell Biology of Cancer is certainly a departure for ASCB, which has never held a one-day meeting like this—11 leading-edge researchers speaking on the cancer­–cell biology nexus in a series of 35-minute talks, interleaved with roundtable discussions, networking, and lunch. Self-contained and capped at 150 attendees, the doorstep meeting will be held at the very threshold of ASCB’s big Annual Meeting, which will open the same day and in the same place, San Francisco’s Moscone Convention Center on Saturday, December 3.

 

It will also be a fitting arrival, say the meeting’s organizers, because the concept behind the ASCB doorstep is to bring modern cancer research back to where it began—in the molecular, cellular, and genetic biology of the cell. Alan Ashworth of the University of California, San Francisco (UCSF), who is the co-organizer with Ira Mellman of Genentech, points to the recent flowering of new cancer therapies derived from decades of basic cell biology research. The benefits and impact on clinical practice are still to come, Ashworth says. “Many cancers are still diagnosed by pathologists who look down a microscope at a sample stained with some brown stuff and say, ‘That’s cancer Type A’,” Ashworth says. “Often it may look like Type A and everyone agrees that it’s Type A but when you look at the molecular make-up, it’s Tumor B. We’re going from that 19th century view of cancer being diagnosed with a microscope to a 21st century view of cancer based on the molecular make-up and from that, what is the prognosis?’

 

The media are suddenly full of jubilant news about breakthrough cancer treatments, says Ashworth. “But it’s premature. We’ve seen some promising results in immune therapy. We’ve seen some reasonable results with targeted therapy. But to this day there are still millions of people dying of the disease. We’ve chipped away at it but if we’re going to get more people to respond and to get durable responses, it’s going to take a lot more effort.”

 

He continues, “We think we’re getting to know how to treat cancer but the reality is that we still know very little about the cellular underpinnings of cancer. That’s why we need to think about these intersections.” The line-up of speakers for ASCB’s first doorstep is simply stellar, Ashworth admits. “It seems injudicious to pick out any one in particular. All of these people are doing such interesting stuff.”

 

Taking that risk, the ASCB doorstep line-up begins with Ashworth’s co-organizer, Ira Mellman, who will present the hottest “new” (if decades in the making) therapeutic approach—cancer immunotherapy. Mellman made his research mark in the 1990s at Yale where he and Ari Helenius discovered the endosome, a critical component in cellular secretion and recycling. In 2007, Mellman left Yale for Genentech where he is now the Vice President for Cancer Immunology.

 

Exploring the critical differences in self-renewal between normal and cancer stem cells will be Sean J. Morrison of the University of Texas, Southwestern Medical Center/HHMI. Using her formidable background in computational genetics, Aviv Regev of MIT/Broad Institute/HHMI will explain how her lab is using single-cell genomics to analyze individual tumor cells, building toward what she hopes will be a new kind of tumor cell atlas. Joan Brugge of Harvard Medical School will confront the invisible elephant in cancer therapeutics—resistance—and describe what cell biology reveals about the genetic and phenotypic heterogeneity within individual tumors driving it.

 

Credit: National Institute of Allergy and Infectious Diseases, National Institutes of Health

T cells are utilized in new cancer immunotherapies. One t cell shown here from a colorized scanning electron micrograph. Credit: National Institute of Allergy and Infectious Diseases, National Institutes of Health

More on the immunology revolution will come from Shannon Turley, another academic who left Dana-Farber for a career in biotech at Genentech. The University of California, San Diego, lab of Michael Karin is at the leading edge of research into hepatocellular carcinoma, one of the world’s most common malignancies. Karin is homing in on what he believes is a key driver, a misfolded autophagy adaptor protein that in liver cancer pile up in aggresomes.

 

Discoveries about the powerful impact of the extracellular matrix on breast cancer opened the field of noncellular cell biology and no one has taken extracellular exploration further than UCSF’s Valerie Weaver. Her lab, which probes stromal­–epithelial interactions, is located in UCSF’s Center for Bioengineering and Tissue Regeneration, which in itself is an indication of the wildcard nature of the new cancer cell biology. The CV of Melody Swartz is another example. Swartz holds dual appointments in bioengineering at the University of Chicago and the École Polytechnique Fédérale de Lausanne in Switzerland. Straight out of college, Swartz won a Watson Fellowship to study technological impact in Micronesia. In 2012, she won a MacArthur Foundation “Genius” grant. Swartz will present her analysis of lymphatic function, a process deeply implicated in chronic inflammation and cancer metastasis but not well studied because it’s part cell biology and part fluid dynamics.

 

From the University of Edinburgh comes Jeffrey W. Pollard, who helped unmask the double nature of macrophages in cancer. Macrophages were long considered protectors, vital to the immune system, wound healing, and cellular housekeeping until Pollard demonstrated that in cancer, macrophages were coopted into promoting tumor growth and metastasis. In his session, Pollard will explain how macrophages shift from physiological regulators to pathological accomplices. The advent of rapid, affordable genomic tumor sequencing has thrown the field of cancer genetic into hyperdrive. Charles W. M. Roberts of St. Jude’s Children’s Research Hospital will show how new data have thrown new light on defects in chromatin remodeling, particularly through his work on a critical tumor suppression complex now linked to 20% of all cancers.

 

Which brings the doorstep list back to Ashworth himself. As a young researcher, Ashworth played a key role in the historic discovery in 1995 of the BRCA2. With BRCA1, they were the first genes directly linked to a high risk for breast cancer in a subset of the population. Ashworth, who came to USCF in 2015 to head the Helen Diller Family Comprehensive Cancer Center after 15 years in London with the Institute for Cancer Research, has pursued what he calls “BRCAness” ever since. Rather than a particular genetic defect, BRCAness is a weakness in a molecular pathway that governs DNA repair so that any cell that has a defect in that pathway should be equally susceptible, he says. Taking advantage of the flood of new data from tumor sequencing, Ashworth’s lab has identified BRCAness in 20% of treatment-resistant prostate cancers, 40% of ovarian cancers, and 5-10% of a range of other cancers.

 

Ashworth is excited by the very idea of having all these leading lights from so many subfields and cross-disciplines in the same room. “This is what happens when you get (ASCB president) Peter Walter to ask people to come. People got it immediately and nearly everyone said yes,” Ashworth recalls. “There was no arm twisting, plus we had Ira (Mellman). Ira knows everybody.”

 

About the Author:


John Fleischman was the ASCB Senior Science Writer from 2000 to 2016. Best unpaid perk of the job? Working with new grad students and Nobel Prize winners.