AACR 2014 conference preview: Progressing toward a cure

Rapid advances in epigenomics, immunology and cancer metabolism create an atmosphere of optimism at this year’s AACR annual meeting

Lloyd Dunlap
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105th American Association for Cancer Research (AACR) Annual Meeting
San Diego Convention Center
April 5-9, 2014

SAN DIEGO—The theme of the 2014 annual meeting of the American Association for Cancer Research (AACR) is “Harnessing Breakthroughs, Targeting Cures,” and when you talk to Dr. Scott W. Lowe, this year’s AACR program committee chairperson, it is easy—and not a misconstruction—to get the impression that the end is near. That finally, more than 40 years after President Richard Nixon declared his “war on cancer,” we are close to achieving victory—a step at a time, certainly, but now with a sense of inevitability. As AACR President Dr. Charles L. Sawyers puts it, “Until recently, there might be a significant advance in cancer research every few years; now it’s every few months—or less.”
 
This startling increase in the frequency of notable advances is primarily due to new technology for examining cancer genomes, Sawyers believes. “We are discovering new mutations in types of genes we would have never imagined a few years ago,” he notes. “For example, mutations in genes that block control of RNA splicing.” The drug development industry is, with increasing effectiveness, targeting cancer-causing genes, he says, and deploying new chemical compounds and antibodies that target these genes.
 
Although the ‘war’ continues on innumerable fronts, from basic research to translational research to clinical research, there are three areas of advancement that will be center stage at AACR 2014: epigenetics, immunology and cancer metabolism. “
We know what happens to DNA in cancer,” Lowe says, “Now epigenetics—the non-genetic control of gene expression—is filling gaps in our knowledge and hints that the chromatin, the combination or complex of DNA and proteins that make up the contents of the nucleus of a cell, can be targeted therapeutically.”
 
Cancer immunology has “exploded,” Lowe states. “There has been the hope for many years that the immune system could be harnessed to fight cancer,” he observes. “Melanoma is one example. Immunological approaches promise to act more broadly than vaccines,” he notes. Chimeric antigen receptors (CARs) are a separate but related approach to enhancing the immune response. These receptors can be used to graft a monoclonal antibody onto T cells which are then removed from a patient and modified to express receptors for that patient’s specific tumor type. The T cells are then reintroduced into the patient and recognize and kill the cancer cells.
 
Changes that occur in cancer metabolism have been widely ignored, according to Lowe, but may be “intimately and directly involved” in disease progression in brain cancer, for example. He cites isocitrate dehydrogenase (IDH1 and 2) as an enzyme that is mutated in cancer and might be a target for therapy.
 
Lowe notes that genomics and next-generation sequencing (NGS) have been hot topics for a decade. “Now NGS has allowed us to sequence cancer cells and we’ve discovered that cancer is heterogeneous even within a single person’s tumor.” This circumstance, he suggests, is important in how cancers evolve and metastasize, making a strong case for therapies that use a combination of drugs.
 
What it means for AACR 2014
The combination drug approach will be a major topic of Sawyers’ presidential address. “Drug resistance has long been problematic in cancer therapy,” he tells DDNews, “and this defines the need for us to more aggressively utilize combinations of drugs that can overcome this resistance through differing mechanisms of actions and targets. To date, the process of developing single agents has been a deterrent to developing more effective combinations.”
 
“We are at a unique time in cancer research,” Lowe stresses, “where big advances and improvements are likely to be forthcoming. It is clear that recent progress against cancer will lead to even greater opportunities for the prevention, treatment and cures for all types of cancer as we become more entrenched in the era of precision medicine. We are confident that attending the AACR annual meeting will give attendees renewed energy, inspiration and focus in their work. Our expectations have become probabilities. Will they soon be realities? Why not?”
 
As Sawyers notes, “This meeting is the most important venue for hearing about the latest breakthroughs, interacting with colleagues and establishing new collaborations. Five days, 18,000 attendees and no one will be bored.”
 
Lowe points out that, as always, the  AACR Annual Meeting 2014 will highlight the latest and most exciting discoveries in every area of cancer research, and it will provide a unique opportunity for investigators from all over the world to meet, network and forge new scientific interactions. “We will also continue to hold several sessions that will feature presentations of new data on cutting-edge clinical trials along with commentaries on the science behind the trials and the implications of these trials for improved patient care,” he notes. “Along with the hundreds of invited talks, we will feature over 6,000 proffered papers by researchers from all over the world. We want to thank the Program Committee co-chairpersons for their incredible expertise, dedication and guidance in shaping an innovative program that will be both enjoyable and educational.”
 
Five NextGen Stars
“An important new feature of the AACR Annual Meeting 2014 will be to include podium talks by so-called ‘NextGen Stars’ in cancer research in several of the major sessions,” Lowe points out. Five early career investigators were selected from 77 competitive applications. These NextGen Stars will present their work in major symposia and current concepts sessions. They will have 15 minutes to present, plus an additional five minutes for discussion. All applicants were AACR associate members or active or affiliate members who are not above the level of assistant professor or equivalent.
 
As part of the NextGen Stars feature, Andrea Bertotti of Italy’s University of Turin will present “Rational drug combinations to improve anti-EGFR targeted therapies in metastatic colorectal cancer” in the Novel Approaches for Understanding the Biology of Colorectal Cancer session, chaired by Dr. Raju Kucherlapati.
 
In addition, Priscilla K. Brastianos of Massachusetts General Hospital in Boston will present “Genomic characterization of 101 brain metastases and paired primary tumors reveals patterns of clonal evolution and selection of driver mutations” in the Novel Mechanisms of Metastasis session, chaired by Dr. M. Mark Taketo.
 
Brooke M. Emerling of Weill Cornell Medical College and New York-Presbyterian Hospital is delivering the talk “Depletion of a putatively druggable class of phosphatidylinositol kinases inhibits growth of p53 null tumors,” which will be part of the Synthetic Lethality session, chaired by Dr. Rene Bernards.
 
Maurizio Scaltriti of Memorial Sloan-Kettering Cancer Center in New York has an address titled “Blockade of EGFR and HER3 enhances PI3K/Akt anti-tumor activity in triple negative breast cancer,” which is part of the Breast Cancer: Progress in Translational Research session, chaired by Carlos L. Arteaga.
 
Finally, David T. Ting, of the MGH Cancer Center/Harvard Medical School in Charlestown, Mass., will present “Diversity of circulating tumor cells in a mouse pancreatic cancer model identified by single cell RNA sequencing” in the Single Cell Analysis of the Tumor session, chaired by Dr. James B. Hicks

AACR NEWS BRIEFS
 
AACR opens Shanghai office
 
PHILADELPHIA—On World Cancer Day in February, AACR announced that it plans to open a China office in Shanghai to better support and promote collaboration among cancer researchers around the world. AACR President Dr. Charles L. Sawyers will formally announce and elaborate on these plans during the annual meeting.
 
“Defeating cancer around the world is a high priority for the AACR, and it will require a global effort,” said Dr. Margaret Foti, CEO of the AACR. “Because cancer has no borders, international collaborations are urgently needed to achieve the new scientific breakthroughs that will lead to cures. The mission of the AACR office in China is to stimulate innovative international collaborations by building bridges and exchanging information on the latest research developments between laboratory and clinical researchers in China, across the Asia Pacific region and other sites around the world where cancer research is being actively conducted to stem the tide of cancer incidence and mortality.”
 
The AACR’s China office is the latest step the organization has taken to advance cancer research around the world. AACR membership now includes more than 34,000 laboratory, translational and clinical researchers, population scientists, other healthcare professionals and cancer advocates residing in 97 countries. Thirty-one percent of the AACR’s members are located outside the United States, and 12 percent are in Asia. Later this year, AACR will host the first-ever “Best of AACR” meeting at its Shanghai facility, featuring the top 20 speakers from AACR 2014 at a two- to three-day meeting designed to engage both younger Chinese cancer scientists and the leaders in the oncology community as well.
 
2014 Rally for Medical Research
 
WASHINGTON, D.C.—AACR and its Washington, D.C., office will again sponsor a Rally for Medical Research in 2014. This Capitol Hill Day event will continue the momentum established in 2013, when more than 200 national organizations came together in support of the event. The purpose of the rally is to call on U.S. policymakers to make funding for National Institutes of Health a national priority and raise awareness about the importance of continued investment in medical research that leads to “More progress, more hope and more lives saved.”
 
Last year on April 8, the first of three such rallies was attended by just under 10,000 advocates who convened on the steps of Carnegie Library in Washington, D.C. Two subsequent events on September 17 and 18 included a Congressional reception with participation by more than 200 AACR partnering organizations who hosted a reception in the Capitol Visitors Center. On Sept. 18, Rally for Medical Research Capitol Hill Day, almost 300 people from more than 40 states convened on Capitol Hill to meet in more than 200 congressional offices, including 80 of the 100 senators’ offices.
 

ADDITIONAL AACR 2014 PRE-SHOW COVERAGE:
 
Plenary Sessions
On Saturday, April 5, a full program of educational sessions, methods workshops, meet-the-expert sessions, and award lectures will be presented beginning at 8 a.m. The opening ceremony and official opening plenary session will take place on Sunday morning, April 6. The meeting will conclude at 1 p.m. on Wednesday, April 9. The plenary sessions are held each day.
 
Sunday, April 6:
Opening Plenary Session: Harnessing Breakthroughs, Targeting Cures
Session Chairperson: Scott W. Lowe, Memorial Sloan-Kettering Cancer Center, New York
  • “Transcriptional and epigenetic control of tumor cells,” by Richard A. Young, MIT Whitehead Institute for Biomedical Research, Cambridge, Mass.
  • “The two faces of p53: Tumor suppressor and oncogene,” by Carol L. Prives, Columbia University, New York
  • “New lymphoma therapies based on functional and structural genomics,” by Louis M. Staudt, National Cancer Institute, Bethesda, Md.
  • “Diet and cancer: Status report in 2014,” by Walter C. Willett, Harvard School of Public Health, Boston
  • Also, an as-yet-to-titled presentation by Roger M. Perlmutter, Merck Research Laboratories, Whitehouse Station, N.J.
 
Monday, April 7:
Targeted Immunotherapy: Mobilizing the Immune System against Cancer
Session Chairperson: Suzanne L. Topalian, Johns Hopkins Kimmel Comprehensive Cancer Center, Baltimore, Md.
  • “Engineering T cells for cancer: CARs in the clinic,” by Carl H. June, Abramson Cancer Center of the University of Pennsylvania, Philadelphia
  • “Investigating inhibition of the CD47 ‘Don't Eat Me’ signal to enable tumor phagocytic removal and augmented cross presentation to T cells, by Irving L. Weissman, Stanford University School of Medicine
  • “The curative potential of T cell transfer therapy for patients with cancer, by Steven A. Rosenberg, National Cancer Institute, Bethesda, Md.
  • “Immune modulation for cancer therapy: Assessing antagonists and agonists, by Jedd D. Wolchok, Memorial Sloan-Kettering Cancer Center, New York
 
Tuesday, April 8
Novel Therapeutic Combinations in Cancer: Principles and Practice
Session Chairperson: Levi A. Garraway, Dana-Farber Cancer Institute, Boston,
  • “Evolutionary dynamics of cancer in response to targeted therapy, by Martin Nowak, Harvard University, Cambridge, Mass.
  • “Combination therapies for lung cancer: Opportunities and challenges, by Pasi A. Jänne, Dana-Farber Cancer Institute, Boston
  • “Combining immunotherapy and targeted therapy for melanoma, by Antoni Ribas, UCLA Medical Center
  • “Combinatorial approaches to prevent compensatory pathways activation, by José Baselga, Memorial Sloan-Kettering Cancer Center, New York
 
Wednesday, April 9
Cellular and Molecular Heterogeneity of Cancer
Chairperson: Suzanne J. Baker, St. Jude Children's Research Hospital, Memphis, Tenn.
  • “Extent of subclonal diversification in primary and metastatic breast cancer, by Peter J. Campbell, Wellcome Trust Sanger Institute, Cambridge, United Kingdom
  • “Dissecting cellular heterogeneity in breast cancer, by Jane E. Visvader, Walter and Eliza Hall Institute of Medical Research, Victoria, Australia
  • “Clonal heterogeneity in acute myeloid leukemia, by Timothy J. Ley, Washington University School of Medicine, St. Louis
  • “Where lies the heterogeneity in GBM?” by Luis F. Parada, UT Southwestern Medical Center, Dallas
 
 
AACR Special Conferences
 
These conferences present unique opportunities to interact with the world’s leading experts and discuss the latest findings in rapidly developing areas of cancer research. Conferences are relatively small (150 to 400 attendees) to allow ample time for discussion and networking. These formal and informal discussions lead to new collaborations among investigators around the world and major advances in knowledge.
 
AACR Special Conferences focus on emerging areas of cancer research each year with the typical program lasting two to four days. Recent programs have focused on cancer epigenetics, molecular epidemiology, EMT, protein translation and cell death mechanisms. A recurring series of special conferences focuses on the basic, clinical and translational aspects of various cancers, including breast, prostate, lung and colon cancer. Programs typically feature several plenary sessions, one or two keynote talks from thought leaders in the field and one or two poster sessions and social events for networking.
 
 
AACRcentral at the 2014 Annual Meeting
 
Whether you’re catching up on email in the internet café or networking with colleagues in one of several resource rooms, you’ll find AACRcentral to be an integral part of your annual meeting experience. Located in the heart of the exhibit hall, AACRcentral brings together valuable services and resources for the benefit of annual meeting attendees. While you’re there, you can also stop by the AACR exhibit booth to speak with AACR staff, learn more about the meeting’s programs and events, become a member or pick up one of AACR’s journals.
 
 
 
 
Centers of attention
 
The AACR has a number of centers to serve the needs and interests of meeting attendees, from membership to networking to careers and more.
 
AACR Membership Centers
The AACR membership centers provide a place where members can obtain information regarding their membership, join association groups within the AACR, update contact information, pay annual dues, transfer categories of membership and become familiar with new membership services. Nonmembers are encouraged to visit the membership centers to submit an application for membership. The AACR is also eager to support the exchange of knowledge and research with investigators who are located in countries with emerging economies. (Significantly reduced membership dues are available for these investigators.) Visit the membership centers located in AACRcentral and the registration area to learn more about these and other opportunities available through the AACR.
 
MICR Networking and Resource Center
The Minorities in Cancer Research (MICR) Networking and Resource Center, located in AACRcentral, hosts meet-and-greet opportunities with prominent investigators and provides meeting attendees with a comfortable and social environment for networking one-on-one and in small groups. All MICR members and annual meeting registrants are encouraged to visit the MICR Networking and Resource Center to learn about AACR and MICR programs, awards, funding and more.
 
WICR Networking and Resource Center
The Women in Cancer Research (WICR) Networking and Resource Center in AACRcentral is the location for networking with members of the WICR Council, WICR scholars and members of WICR. Annual meeting attendees and WICR members are also invited to use the center during exhibit hours for networking and to learn more about professional advancement opportunities and other programs of interest.
 
Associate Member Resource and Career Center
The Associate Member Resource and Career Center, organized by the Associate Member Council, is open to graduate students, medical students, medical residents and postdoctoral and clinical fellows regardless of membership status. The center provides an informal place for early-career scientists to connect with colleagues, plan their time at the meeting and learn more about funding and other professional advancement opportunities. Several special programming sessions intended for early-career scientists are hosted in this area that allow for interactive discussion with other researchers and the opportunity to explore different career interests. Limited seating is available on a first-come, first-served basis for the special interest sessions. Scholar-in-training awardees can also pick up their checks and welcome packets at this location.
 
AACR CancerCareers.org Center
The CancerCareers.org Center is where researchers and clinicians at all career levels come for the right opportunities and where recruiters from academia, industry and government can meet and recruit the right talent. Visit the Center at the AACR Annual Meeting 2014 or online anytime at www.CancerCareers.org.
 
 
Meet the Mentor: Undergraduate focus
 
The AACR Science Education Committee is pleased to present a series of informal lectures presented by outstanding investigators in the field of cancer research for undergraduate students. Discussion topics include guidance on professional development, advice on career paths and the pursuit of a career in cancer research. Students should bring their questions to these interactive sessions in the amphitheater located in AACRcentral.
 
 
AACR Amphitheater
The AACR Amphitheater hosts a variety of sessions, including Meet the AACR CEO, Meet the AACR President and Meet the Research Pioneer sessions, which provide a special opportunity to meet esteemed researchers in a small-group setting to discuss their career paths and their vision for the future of their field. Limited seating is available on a first-come, first-served basis.
 
 
Current concepts in organ site research
 
A number of “current concept” sessions will be held during AACR 2014, focusing on the specific organs involved:
  • Breast Cancer: Progress in Translational Research
  • The Dharma Master Jiantai Current Concepts in Lung Cancer Session: Novel Targets in Non-Small Cell Lung Cancer
  • From Rags to Riches? Prostate Cancer in 2014
  • Genetic Lesions and Therapeutic Opportunities in Acute Myeloid Leukemia
  • Hepatocellular Carcinoma
  • Invasive Bladder Cancer: Genomic Insights and Therapeutic Promise
  • Lymphoid Malignancies
  • Melanoma Therapeutic Targeting and Drug Resistance
  • Neuroendocrine Cancer: Current Molecular and Genomic Strategies in Diagnosis and Management
  • New Horizons in Sarcoma Research
  • Novel Approaches for Understanding the Biology of Colorectal Cancer
  • Pancreatic Cancer
  • Pediatric Brain Tumors: Novel Molecular Insights and Preclinical Studies
  • A Systems Approach to Ovarian Cancer
 
Educational Forums
A number of educational forums will be held at this year’s AACR meeting on subjects as diverse as genomics, crowdsourcing, training and mentoring and radiotherapy. Planned offerings are:
  • Antioxidant to Pro-Oxidant Therapy for Cancer
  • Controversies and Challenges Posed by Incidental Findings from Tumor Genome Analysis
  • Crowdsourcing Cancer Research: The Role of Quantitative Challenges
  • Genomics: How Deep Is a Deep Enough Dive?
  • How to Achieve a Cancer Knowledge Commons Database of Cancer Genetics
  • MICR Forum: The Role of Training and Mentoring in Navigating a Successful Cancer Research Career
  • Plasticity vs. Hierarchy in Tumors
  • Putting Molecular Science into Clinical Trials
  • Screening for Lung Cancer: Do We Know the Way Forward?
  • Stereotactic Body Radiotherapy: Dose (Physics) or Biology?
  • Targeting Autophagy in Cancer: Promise or Peril?
  • What Is (Are) the Mechanism(s) by Which the p53 Protein Enforces Tumor Suppression?
 
 

Lloyd Dunlap

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