AACR 2020 Show Preview: Crafting better cancer care

The AACR Annual Meeting covers the best in cutting edge cancer research and care

Mel J. Yeates
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American Association for Cancer Research (AACR)
AACR Annual Meeting 2020
April 24-29, 2020
San Diego Convention Center
San Diego, California
 
UPDATE March 10 6:00 p.m.ET
The AACR 2020 meeting has been cancelled/postponed. For more information, click here.
 
NOTE: As of March 10, when this story was posted online at midday, there was talk of the AACR meeting perhaps becoming a virtual meeting instead of a physical one because of concerns around the COVID-19 coronavirus. However, no final determination had yet been made on that front as of the posting of this show preview on our website. – Jeffrey Bouley, Chief Editor
 
Crafting better cancer care
The AACR Annual Meeting covers the best in cutting edge cancer research and care
Mel J. Yeates
 
This spring, the 111th Annual Meeting of the American Association for Cancer Research (AACR) will be held in California from April 24-29 at the San Diego Convention Center. AACR anticipates the attendance of over 24,000 scientists, clinicians and advocates from all over the world, gathering the best minds in research and medicine to cover population science, cancer prevention, cancer biology, translational and clinical studies, survivorship and advocacy.
 
This years theme for the meeting is Turning Science into Lifesaving Care,” and the scientific program includes an outstanding roster of world-class speakers, hundreds of invited talks and more than 6,000 proffered papers. Presentations will span the entire field of cancer research, highlighting basic, translational and clinical research on important topics such as immunotherapy, science policy, targeted therapy, artificial intelligence, liquid biopsy, early detection, cancer interception, prevention, survivorship and cancer health disparities,” according to an AACR news release.
 
“Following the success of last year’s meeting, we are again offering two days of educational programming, beginning at 3 p.m. on Friday, April 24, and continuing through Saturday, April 25. This year will feature our largest education program to date, with over 70 educational sessions and methods workshops covering all areas of cancer science and medicine,” says Dr. Antoni Ribas, AACR’s annual meeting program chair and president-elect. “Access to the complete educational program is available by adding the Educational Program Pass ($50 for AACR members, $75 for nonmembers) to the meeting registration.”
 
“The popular ‘New Drugs on the Horizon’ session series has been expanded this year to three sessions that will be held on Sunday, April 26 and Monday, April 27,” he continues.
 
The New Drug sessions will give meeting attendees the opportunity to learn about newly disclosed drug candidates (both small molecules and biologics) which have recently entered Phase 1 clinical trials. Presentations will note the chemical structures of the drug candidates, and reveal highlights of the drug discovery programs and plans for ongoing clinical development.
 
Ribas highlights for DDNews’ readers the aforementioned “New Drugs on the Horizon” sessions, as well as four Clinical Trial Design Method workshops entitled “Novel Approaches and Methods in Clinical Trial Design,” “Clinical Trials Issues with Molecularly Targeted Agents,” “Clinical Development of IO Agents” and “Trial Design for Early Cancer Detection.”
 
Ribas also points out two Educational Sessions that may be of particular interest to our readers: “Chemistry to the Clinic: Part 1: Lead Optimization Case Studies in Cancer Drug Discovery” and Chemistry to the Clinic: Part 2: Irreversible Inhibitors as Potential Anticancer Agents.”
 
In “Chemistry to the Clinic: Part 1,” presenters will share four recent case studies highlighting successful strategies for identifying hits, leads and candidates for important cancer targets and pathways that have historically been considered intractable. “Chemistry to the Clinic: Part 2” will provide a broad look at covalent probe compounds and drug development, including a historical perspective, examination of warheads and electrophilic amino acids, the role of chemoproteomics and case studies.
Ribas indicates two offerings in the Major Symposia program that may hold insight for our readers: “ACCELERATE-ing Pediatric Oncology Drug Discovery and Development” and Drugging KRAS.”
 
In the first session, stakeholders from the AACR Pediatric Cancer Working Group, the U.S. Food and Drug Administration and others will update on progress toward full implementation of the RACE for Children Act, including a discussion of new upcoming requirements for submission of Initial Pediatric Study Plans for cancer drugs directed at targets potentially relevant to pediatric cancers. The symposium will also explore the global potential of the ACCELERATE platform, which provides a forum for stakeholder groups to discuss overarching issues in the development of innovative anticancer medicines.
 
The second symposium will briefly summarize information on drugs targeting KRAS G12C that are now in the clinic, and early results which show promising activity. But the main focus of the session will be the next generation of KRAS inhibitors, targeting different alleles of KRAS and using different approaches like pan-KRAS selective inhibitors and drugs that block KRAS processing. Also slated for discussion: combination therapies based on preclinical experiments with CRISPR-based screens and combinations of potential small molecules, as well as an assessment of the benefits and challenges of targeting KRAS in different types of cancer.
 
Ribas also notes that the AACR meeting has “a number of sessions focused on single-cell analysis, early detection, imaging, unique cancer models, etc.”
 
“At the end of the conference days we will have a series of forums, where experts will discuss cutting-edge topics in an open format,” Ribas adds. “These are great opportunities to participate in discussion with top experts in different fields about scientific topics that are of timely interest.”
 
The forums include:
  • Are Antitumor T Cells Exhausted or Dysfunctional? Does it Matter?
  • Are There Cancer Stem Cells?
  • Biostatistics Debate: Should Science Be Guided by P-Values?
  • Cancer Cell Dormancy: The Current Paradigm and the Challenges Ahead to Develop New Therapies
  • CAR T-Cell Therapy or T-Cell Engager?
  • Data Science and Machine Learning: Will They Revolutionize Cancer Care and Research?
  • Disparities in Cancer Outcomes: Biology, Access, and Equity
  • Embracing Entrepreneurship in Cancer Research
  • FDA Vision 2025 Forum
  • Microbiome Pandemonium: Checkpoints and the Microbiome
  • Minorities in Cancer Research Forum
  • The Myths and Realities of the Abscopal Effects
  • Patient-Derived Models for Cancer
  • What Is the Role for Oncolytic Viruses in Cancer Treatment?
The AACR is sensitive to the current coronavirus concerns, and states that the organization is closely monitoring the continuing developments ... We want to assure colleagues planning to attend any upcoming AACR national or international meetings that safety and security are our top priorities. At this time, there is no plan to cancel or postpone any scheduled AACR meetings. The AACR is tracking all travel restrictions issued by the U.S. government, as well as information and guidance from the U.S. Centers for Disease Control and Prevention and the World Health Organization. We will provide further updates as events warrant.” 
 
As for next year’s meeting? “We already have a stellar Program Committee in place. We will be in Washington, D.C.—an exciting year, as we will also be celebrating the [50th] anniversary of the National Cancer Act,” Ribas concludes.
 
Educational Sessions
 
Friday, April 24
  • Benign Cells as Drivers of Cancer Progression: Fat and Beyond
  • Data-Driven Approaches for Choosing Combinatorial Therapies
  • Functional Precision Medicine: Techniques, Uses, and Challenges
  • HPV and Cancer: New Insights into Carcinogenesis and Therapy
  • Know Thy Organ: Lessons Learned from Lung and Pancreatic Cancer Research
  • Molecular Imaging in Cancer Research
  • Overcoming Therapeutic Resistance: Challenges and Opportunities
  • Targeted Protein Degradation: Target Validation Tools and Therapeutic Opportunity
  • Unexpected Guests in the Tumor Microenvironment: The Tumor Microbiome 
  • Wound Healing that Never Actually Heals: The TME in Cancer Progression
Saturday, April 25
  • Analysis of Biological Imaging Data Using Machine Learning
  • Artificial Intelligence and Machine Learning from Research to the Cancer Clinic
  • Cancer Epigenetics
  • Cancer Increases in Younger Populations – Where Are They Coming From?
  • Cancer Stem Cells and Therapeutic Resistance
  • Carcinogens at Home
  • Chemistry to the Clinic: Part 1: Lead Optimization Case Studies in Cancer Drug Discovery
  • Chemistry to the Clinic: Part 2: Irreversible Inhibitors as Potential Anticancer Agents
  • Chemistry to the Clinic: Part 3: Next-Generation Medicines on Clinically Useful Targets
  • The Clinical Proteomic Tumor Analysis Consortium: Resources and Data Dissemination
  • Communication to Patients
  • EMT Still Matters: Let’s Explore!
  • Engaging the Oncology Community to Advance Regulatory Science- FDA’s Project Renewal and Project Socrates
  • Engineering and Physical Sciences Approaches in Cancer Research, Diagnosis, and Therapy
  • Evaluating Immunocompetent Models to Build Greater Success in Cancer Immunotherapy
  • Evolutionary Pressures Drive Cancer Emergence
  • The Evolving Role of the Pathologist in Cancer Research
  • Exceptional Responders and Long-Term Survivors
  • Exploiting Metabolic Vulnerabilities in Cancer
  • Extracellular Vesicles in Cancer
  • Host-Microbiome Interactions in Inflammation and Cancer
  • Hot Topics in Oncology Regulation
  • How Many R’s in Radiobiology?
  • Immunotherapy, Immune Evasion in Myeloid Malignancies, and Therapeutic Implications
  • Informatics Technologies for Cancer Research
  • Metabolism and Tumor Microenvironment
  • Noncoding RNA in Cancer Progression
  • Novel Approaches in Single-Cell Analysis
  • Novel Diagnostic Approaches for Cancer Early Detection
  • Novel Strategies in Cancer Immunotherapy, The Next Generation of Targets for Anti-Cancer Immunotherapy
  • Novel Targeted Agents and Mechanisms of Resistance
  • One of These Things Is Not Like the Other: The Many Faces of Senescence in Cancer
  • Radiation and Immunotherapy
  • Recent Advances in Applications of Cell-Free DNA
  • Rewiring of the Tumor Microenvironment Epigenome for Cancer Therapy
  • Sex Differences in Cancer
  • Stress Adaptation and Resiliency in Cancer
  • The Three-Dimensional Cancer Genome
  • Tumor Cell Dormancy
  • Tumor Endothelium: The Gatekeepers of Tumor Immune Surveillance
  • Tumor Immunology and Immunotherapy for Non-immunologists: Innovation and Discovery in Immune-Oncology
  • Tumor Immunology and Immunotherapy for Non-immunologists: Roundtable Discussions
  • Where To Screen: SubQ versus Orthotropic Metastatic Sites
 
Methods Workshops
 
Friday, April 24
  • Cancer Vaccines
  • Immunophenotyping in Population-Based Studies Using Omics Data
Saturday, April 25
  • Clinical Trial Design: Part 1: Novel Approaches and Methods in Clinical Trial Design
  • Clinical Trial Design: Part 2: Clinical Trials Issues with Molecularly Targeted Agents
  • Clinical Trial Design: Part 3: Clinical Development of IO Agents
  • Clinical Trial Design: Part 4: Trial Design for Early Cancer Detection
  • Data Resources for Cancer Research
  • Emerging Models: Bring in the Engineers
  • High-Dimensional Imaging of Immune and Tumor Cells in Human FFPE Tissue
  • High-Throughput Screens for Drivers of Progression and Resistance
  • Implementation Science Methods for Cancer Prevention and Control in Diverse Populations: Integration of IS Methods in Care Settings
  • Interpretation and Analysis of Single-Cell Data from Bench to Bedside
  • Methods for Data Integration Approaches to Accelerate Cancer Early Detection
  • Minimal/Measurable Residual Disease: How to and Implications in Treatment and Trials
  • Models and Methods to Dissect Toxicity in Cancer Treatment
  • Probing the Niche Using Multiple Approaches
  • Translating Genetics and Genomics to the Clinic and Population
 
Plenary Sessions
 
Sunday, April 26
Opening Plenary Session: Turning science into lifesaving care
Chair: Antoni Ribas, UCLA Medical Center
Personal regulome navigation of cancer
Howard Y. Chang, Stanford University
Turning the science of epigenetics into novel cancer early detection and classification approaches
Daniel Diniz De Carvalho, Princess Margaret Cancer Centre
Age against the machine: How changes in the aged tumor microenvironment govern response to therapy
Ashani T. Weeraratna, The Sidney Kimmel Cancer Center at Johns Hopkins School of Medicine
Towards AI-driven cancer precision medicine
Olivier Elemento, Weill Cornell Medical College of Cornell University
Reprogramming human T cells with CRISPR for cancer immunotherapies
Alexander Marson, University of California San Francisco
 
Monday, April 27
Understanding the molecular and microenvironmental determinants of cancer
Chair: Christina Curtis, Stanford University
Pathology from the atomic scale on up
Garry P. Nolan, Stanford University School of Medicine
Harnessing the value of mutational signatures: Causes, mechanisms and clinical applications
Serena Nik-Zainal, University of Cambridge
Clonal hematopoiesis and evolution to hematologic malignancies
Ross L. Levine, Memorial Sloan Kettering Cancer Center
 
Tuesday, April 28
Cancer biology and the changing therapeutic landscape
Chair: Sheila A. Stewart, Washington University
Targeting secreted factors in the tumor microenvironment for pancreatic cancer therapy
Tony Hunter, Salk Institute
Using genetics to select and validate cancer drug targets
William G. Kaelin, Jr., Dana-Farber Cancer Institute
Genetics in cancer care: From family reunions to the frontline of experimental therapeutics
Olufunmilayo I. Olopade, University of Chicago Medicine Comprehensive Cancer Center
 
Wednesday, April 29
Leveraging the immune system in the war on cancer
Chair: Nina Bhardwaj, Icahn School of Medicine at Mount Sinai
Revving up antitumor immune response with cGAS
Zhijan James Chen, UT Southwestern Medical School
Transcriptional networks in tumor-infiltrating T cells
Anjana Rao, La Jolla Institute for Immunology
Targeting regulatory T cells in cancer: From mechanisms to new therapies
Sergio A. Quezada, University College London Cancer Institute
CARs and HIT-CARs: Drivers of synthetic immunity
Michel Sadelain, Memorial Sloan Kettering Cancer Center
 
Major Symposia
  • AACR-Bayard D. Clarkson Symposium on Stem Cells, Leukemia, and the Niche
  • AACR-CSCO Joint Symposium: Single-Cell Analysis—Changing the Landscape of Cancer Research
  • AACR-JCA Joint Session: Tracking Tumor Ecological and Evolutionary Dynamics: From Initiation through Metastasis
  • ACCELERATE-ing Pediatric Oncology Drug Discovery and Development
  • Advances in Cancer Nanotechnology
  • AI (Artificial Intelligence) in Cancer Imaging
  • AI/ML in Cancer Research and Care: Progresses and Opportunities
  • Alternative DNA Repair Pathways and Their Drug Targets
  • The Cancer Dependency Map
  • Cancer Immunometabolism
  • The Clinical Proteomic Tumor Analysis Consortium: Building a Proteogenomic Atlas of Cancer
  • Colorectal Cancer Interception: Immunologic and Pharmacological Advances
  • Cytokine Receptors in Immuno-Oncology: Discovery, Analysis, and Modulation
  • Deubiquitylating Enzymes (DUBs) as Targets for Cancer Therapy
  • Developing Rational Combinations of Targeted Drugs
  • Diet, Clock, and Cancer
  • A Discussion of the U.S. Vaping and Electronic Cigarette (e-cigarette) Epidemic: Understanding the Challenges and Emerging Science Needed to Inform Policy to Protect Public Health
  • Drugging KRAS
  • Engineering and Modulating Natural Killer (NK) Cells for Cancer Immunotherapy
  • Familial Predisposition: Precision Medicine and Targeted Therapy
  • From ‘Omics Data to Prognostic and Predictive Biomarkers
  • Functional Precision Medicine in Cancer
  • Germline Influence on Immunotherapy Outcomes
  • Hypoxia and Genetic Instability
  • Implications of Clonal Hematopoiesis in Human Health
  • Improving Therapy through Normalization of the Tumor Microenvironment
  • International Regulator Panel
  • “itRECIST:” Determining Response from Intratumoral Injection
  • Matrix, Exosomes, and TME Cells in the Metastatic Niche
  • Mechanisms and Biomarkers for Response and Resistance to Immune Therapy
  • Metabolism and Chromatin Deregulation in Cancer and Cancer Heterogeneity
  • The Microbiome in Cancer Therapy: Hype or Hope?
  • Modeling Metastatic Progression in the Mouse
  • Molecular Imaging
  • Neoadjuvant Immunotherapy for Melanoma and Other Cancers
  • New Approaches to Chimeric Antigen Receptor Engineering
  • New Combinations of Targeted Therapies and Immunotherapies
  • Next Frontiers in Adjuvant Therapy
  • Next-Generation Epigenetic Drugs
  • Options and Opportunities for Treating Metastasis
  • Overcoming Practice Challenges that Mitigate Value of Genetic Sequencing for Personalized Therapy in Cancer Care
  • Paracrine Signaling in Cancer
  • Phase Separation, Transcription, and Cancer
  • Presidential Select Symposium: Precision Pediatric Cancer Medicine – A Global Perspective
  • Progress from Personalized Cancer Vaccine Trials
  • Regulatory Considerations for Liquid Biopsy Development
  • A Session with Oncology Center of Excellence Director Richard Pazdur
  • T Cells in Cancer
  • TCR Targeting of Mutational Neoantigens
  • Tumor Cell Plasticity and Resistance to Cancer Therapies
  • Tumor Hypoxia and Genetic Instability: New Mechanisms and New Targets
  • The Tumor Microbiome and Its Role in Oncogenesis and Modulating Therapy Response
  • Under-representation in Clinical Trials and the Implications for Drug Development
  • Using Real-World Data for Regulatory Purposes in the Real World
  • When is Transforming Growth Factor Beta Targetable?
 
Policy Sessions
The AACR sponsors sessions with government leaders, academic researchers, patient advocates, cancer survivors and industry representatives to foster dialogue about the emerging topics of science, health, regulatory science and policy.
 
The sessions are grouped into three tracks:
  • Science and Health Policy
  • Regulatory Science and Policy
  • Science of Survivorship
 
NextGen Stars
The NextGen Stars program provides an exciting opportunity to increase the visibility of early-career scientists at the AACR Annual Meeting and to support the professional development and advancement of those selected as AACR NextGen Stars.
 
Uri Ben-David, Ph.D.
Assistant Professor, Department of Human Molecular Genetics and Biochemistry
Tel Aviv University, Tel Aviv, Israel
 
Joshua J. Breunig, Ph.D.
Assistant Professor, Department of Biomedical Sciences
Cedars-Sinai Medical Center, Los Angeles
 
Marios Giannakis, M.D., Ph.D.
Assistant Professor of Medicine, Medical Oncology
Dana-Farber Cancer Institute, Boston
 
Lee D. Gibbs, Ph.D.
Postdoctoral Fellow, Department of Translational Genomics
Keck School of Medicine of University of Southern California, Los Angeles
Sheng Li, Ph.D.
Assistant Professor, Genomic Medicine
The Jackson Laboratory, Farmington, Conn.
 
Ping Mu, Ph.D.
Assistant Professor, Department of Molecular Biology
The University of Texas Southwestern Medical Center, Dallas
 
Maeve Mullooly, Ph.D., MPH
Research Fellow, Division of Population Health Sciences
Royal College of Surgeons in Ireland, Dublin
 
Cristina Puig-Saus, Ph.D.
Associate Project Scientist, Division of Hematology-Oncology
University of California, Los Angeles
 
Nidhi Sahni, Ph.D.
Assistant Professor, Department of Epigenetics and Molecular Carcinogenesis
The University of Texas MD Anderson Cancer Center, Smithville, Texas
 
Ingunn Stromnes, Ph.D.
Assistant Professor, Department of Microbiology and Immunology
University of Minnesota, Minneapolis
 
Neil Vasan, M.D., Ph.D.
Assistant Attending Physician
Memorial Sloan Kettering Cancer Center, New York
 
Liling Wan, Ph.D.
Assistant Professor, Department of Cancer Biology
University of Pennsylvania, Philadelphia
 
2020 AACR Runners for Research 5K Run/Walk
Whether you’re a walker or a runner, team up with the AACR to advance lifesaving cancer research. Join this event to support more than 200 childhood and adult cancers, and members who lead the effort to prevent and cure cancer. The 5K will be held in San Diego on the Embarcadero Boardwalk.
Saturday, April 25, 7:30 a.m. 
 
Career Fair
Saturday, April 25
9 a.m. to 3 p.m.
Whether you are a research scientist or an employer, the AACR 2020 Cancer and Biomedical Research Career Fair invites you to join this premier recruiting event. If you are a scientist seeking opportunities within academia, government, or industry, you will meet with representatives who are seeking to fill many positions. As an employer, you will have the opportunity to meet with hundreds of prospective candidates. Learn more about the 2020 Career Fair, search for scientific positions, and upload your CV/resume. Employers may also post their open positions.
 
Professional Development Opportunities
Professional and Career Advancement Sessions
These sessions are organized to provide important skills to investigators at all levels, from high school students to junior faculty. Programs for high school students and undergraduates require registration. All other Professional Advancement Sessions are available to annual meeting registrants free of charge, but attendance is limited to AACR members.

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AACR Scientific Achievement Awards
AACR Distinguished Lectureship in Breast Cancer Research, supported by Aflac, Inc.
AACR Distinguished Lectureship on the Science of Cancer Health Disparities
AACR Outstanding Investigator Award for Breast Cancer Research, supported by the Breast Cancer Research Foundation
AACR Award for Lifetime Achievement in Cancer Research
AACR Award for Outstanding Achievement in Basic Cancer Research
AACR Award for Outstanding Achievement in Chemistry in Cancer Research
AACR Princess Takamatsu Memorial Lectureship
AACR Team Science Award
AACR-American Cancer Society Award for Research Excellence in Cancer Epidemiology and Prevention
AACR-Cancer Research Institute Lloyd J. Old Award in Cancer Immunology
AACR-G.H.A. Clowes Award for Outstanding Basic Cancer Research
AACR-Joseph H. Burchenal Award for Outstanding Achievement in Clinical Cancer Research
AACR-Margaret Foti Award for Leadership and Extraordinary Achievements in Cancer Research
AACR-Minorities in Cancer Research Jane Cooke Wright Lectureship
AACR-St. Baldrick’s Foundation Award for Outstanding Achievement in Pediatric Cancer Research
AACR-Waun Ki Hong Award for Outstanding Achievement in Translational and Clinical Cancer Research
AACR-Women in Cancer Research Charlotte Friend Lectureship
Pezcoller Foundation-American Association for Cancer Research International Award for Extraordinary Achievement in Cancer Research
 
Exhibit Hall Hours
​Sunday, April 26
​1 p.m. to 5 p.m.
 
​Monday, April 27
​9 a.m. to 5 p.m.
 
​Tuesday, April 28
​9 a.m. to 5 p.m.
 
​Wednesday, April 29
​9 a.m. to 12 p.m.
 
Future AACR Annual Meetings
April 10-14, 2021
Washington, D.C.
 
April 9-13, 2022
New Orleans, La.
 
April 15-19, 2023
Orlando, Fla.
 
Other Upcoming AACR Meetings
NIH-AACR Cancer, Autoimmunity, and Immunology Conference
March 23-24, 2020
Bethesda, Md.
 
Eighth Annual Symposium on Global Cancer Research (ASGCR2020)
April 17, 2020
Washington, DC
 
Seventh JCA-AACR Special Joint Conference on the Latest Advances in Pancreatic Cancer Research: From Basic Science to Therapeutics
June 9-11, 2020
Kyoto, Japan
 
Second AACR International Meeting: Advances in Malignant Lymphoma: Maximizing the Basic-Translational Interface for Clinical Application
June 25-28, 2020
Boston
 
EORTC-ESMO-AACR Methods in Clinical Cancer Research Workshop
June 26-July 2, 2020
int-Michielsgestel, Netherlands
 
AACR News: A single gene mistake
PHILADELPHIA—The loss of a single copy of the miR15a/miR16-1 gene cluster promoted the initiation and progression of multiple myeloma in mice, according to results recently published in Blood Cancer Discovery.
 
Multiple myeloma is a cancer of antibody-producing plasma cells. It’s preceded by monoclonal gammopathy of undetermined significance (MGUS), in which abnormal plasma cells are present but don’t expand. The detection of an M spike, which indicates the accumulation of an abnormal secreted antibody in the patient’s blood, is a hallmark of both MGUS and multiple myeloma.
 
“The risk of progression from MGUS to malignant multiple myeloma is approximately 1 percent each year, but the factors that contribute to progression are not well understood,” said Dr. Marta Chesi, an associate professor of medicine at the Mayo Clinic. “The purpose of our study was to model genetic risk factors that may contribute to initiation and progression of multiple myeloma. This understanding could eventually allow us to identify the mechanisms that increase the risk of progressing to multiple myeloma.”
 
One copy of chromosome 13 is deleted in around 50 percent of patients with MGUS and multiple myeloma, but the significance of this deletion on prognosis and disease progression remains controversial. Chesi and colleagues hypothesized that individual genes on chromosome 13 may promote disease initiation and/or progression.
 
The authors examined the impact of two genetic loci found on human chromosome 13—Rb1 and miR15a/miR16-1—on disease initiation and progression. Both Rb1 and miR15a/miR16-1 are considered tumor suppressor genes, due to their roles in regulating cellular proliferation. The Rb1 protein is known to be inactivated in many cancers, including multiple myeloma. And a previous study demonstrated that deletion of miR15a/miR16-1 enhances proliferation of human B cells, and deletion of the gene in mice promotes development of another blood cancer, chronic lymphocytic leukemia.
 
In this study, the authors deleted a single copy of either Rb1 or miR15a/miR16-1 in wild-type mice, and in a previously developed transgenic mouse model of multiple myeloma. Deletion of one copy of Rb1 didn’t affect disease initiation or progression, but deleting one copy of miR15a/miR16-1 in wild-type mice significantly accelerated the development of an M-spike. The deletion of one copy of miR15a/miR16-1 also significantly enhanced the aggressiveness of the disease, and led to increased expression of genes that promote cellular proliferation. The authors analyzed a genetic dataset of multiple myeloma patients, and found that deletion of one copy of miR15a/miR16-1 in patient tumors was associated with increased expression of the same cellular proliferation genes that were upregulated in mice.
 
“Losing one copy of the miR15a/miR16-1 gene appears to promote tumor cell proliferation in both mice and patients. For many years, we thought that deletion of chromosome 13 was just a byproduct of other genetic changes in the tumor and that it did not directly affect disease progression,” Chesi noted. “Our study now demonstrates that deletion of chromosome 13, and specifically deletion of miR15a/miR16-1, appears to alter the biology of the tumor. However, the fact that the entire chromosome 13, and not just miR15a/miR16-1, is lost in many cases of MGUS or multiple myeloma suggests that other genes on this chromosome are also likely to be important for pathogenesis.”
 
Chesi is interested in studying DIS3, another gene located on chromosome 13 that is frequently mutated in multiple myeloma. The authors were not able to assess its contribution in this study, due to the lack of relevant mouse models. Another study limitation was the inability to delete Rb1 or miR15a/miR16-1 only in myeloma cells, due to technical restrictions of the mouse model. As a result, these genes were deleted in all cells—including immune cells—which could have led to indirect effects on disease progression, according to Chesi. However, results from additional control experiments indicate that the observed results are unlikely to be indirect, as transplanted tumors behaved similarly in both wild-type and miR15a/miR16-1-deleted mice.
 
AACR News: AACR receives $2 Million from UBS OIF
PHILADELPHIA—The American Association for Cancer Research (AACR) will receive $2 million from the UBS Oncology Impact Fund (UBS OIF), as part of a partnership that supports potentially transformative cancer research.
 
“We are thrilled to receive this incredible gift from the UBS Oncology Impact Fund,” said Mitch Stoller, chief philanthropic officer and vice president of development of the AACR Foundation. “These funds will fuel the essential research needed to accelerate the novel discoveries and potential treatments that will make an important impact not only on the field, but for the patients dealing with this devastating disease.”
 
The UBS OIF is also donating $2 million to the UBS Optimus Foundation to support access to cancer care in emerging markets. The donations come from the performance fees of the UBS OIF, which is managed by MPM Capital. In the future the fund also intends to donate 1 percent of the revenues on treatments from participating companies in which the fund has invested.
“To witness the growth of this critically important collaboration has been so rewarding. We are continually hopeful that this support will catalyze the next wave of advancements in the field, leading us closer to finding new ways to prevent, treat, and potentially cure cancer,” added Christiana Bardon, M.D., MBA, managing director of the UBS Oncology Impact Fund and a trustee of the AACR Foundation. 
 
The AACR plans to announce another grants opportunity funded by the UBS OIF gift later this year. Research under the program must represent a highly innovative approach to a major problem or challenge in cancer research that might not be funded through more conventional channels. Projects are expected to catalyze important advances in cancer research, and should have a potentially transformative impact on future clinical practice.
 

AACR News: Dengue infection could increase leukemia risk
PHILADELPHIA—Compared to individuals without a history of dengue infection, people previously infected with the virus had over twice the risk of developing leukemia, according to the results of a study conducted in Taiwan and published in Cancer Epidemiology, Biomarkers & Prevention.
 
“It has been estimated that approximately 15 percent of human cancers globally are caused by infections, which are potentially preventable,” said Dr. Guey Chuen Perng, a professor of basic medical sciences in the Department of Microbiology at the National Cheng Kung University. “Dengue fever, while usually self-limiting, can result in abnormal hematologic profiles and bone marrow suppression.”
 
“Dengue fever has generally been considered as an acute infectious disease, and the long-term effects of dengue virus infection have seldom been investigated. Our findings suggest that infection with the dengue virus is associated with the diagnosis of leukemia years after acute infection,” added Dr. Cho-Yin Lee, an assistant professor in the Department of Biomedical Engineering at the National Yang-Ming University and radiation oncologist at the Taoyuan General Hospital of the Ministry of Health and Welfare.
 
To investigate if prior dengue infection is associated with leukemia incidence, Perng and colleagues analyzed population-based data from the National Health Insurance Research Database (NHIRD) in Taiwan. Between 2002 and 2011 they identified 12,573 laboratory-confirmed dengue-infected patients. Five individuals without a history of dengue virus infection were selected from the NHIRD for each dengue case, representing 62,865 individuals. Controls were matched by age, sex, area of residence and the calendar year of the index date.
 
After controlling for multiple factors, including monthly income level and comorbidities, researchers found that those with previous dengue infection had over twice the risk of developing leukemia compared with controls. And after analyzing different follow-up periods, Perng and colleagues discovered that prior dengue infection was associated with a higher risk of leukemia among those who had been infected with dengue at least three years prior. The highest risk of leukemia occurred between three and six years after infection with dengue; these patients had more than three times the risk of developing leukemia compared with controls. Those in the dengue cohort were also more likely to live in urbanized areas.
 
“If these findings are validated, the leukemia burden attributable to dengue virus would profoundly increase, especially when we account for the rising rates of dengue virus infection,” Lee stated.
 
The researchers evaluated the association between previous infection with dengue virus and the risk of lymphoma or other non-hematologic malignancies, but no significant associations were found.
 
Because the number of leukemia cases in the dengue cohort was low, the authors were unable to evaluate the association between dengue virus infection and specific leukemia subtypes, noted Lee. The authors were also limited in not being able to control for certain risk factors of leukemia—including lifestyle factors and environmental exposures—as this information was not available in the NHIRD.
 

Mel J. Yeates

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