AACR 2016 Show Preview: The long and winding road

Key areas to be addressed at AACR annual meeting include immunotherapy, epigenetics and newer techniques and tools such as CRISPR

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107th American Association for Cancer Research Annual Meeting 2016
April 16-20, 2016
Ernest N. Morial Convention Center
New Orleans. Louisiana
The long and winding road
Key areas to be addressed at AACR annual meeting include immunotherapy, epigenetics and newer techniques and tools such as CRISPR
NEW ORLEANS—Just about any organization operating in the life-sciences and pharma/biotech realms will tell you that its annual meeting is a “must-attend” event. But in point of fact, if you are pursuing oncology-related research or development, the 107th American Association for Cancer Research (AACR) Annual Meeting 2016 to be held in New Orleans this spring probably is as close to a necessity for your convention rounds in 2016 as any could be.
And so the organizers of AACR 2016 do say this is a must-attend event for cancer researchers and the broader cancer community, with the theme “Delivering Cures Through Cancer Science” reinforcing the inextricable link between research and advances in patient care.
The pathway to cures is not likely to be any more straightforward this year than it ever had been, however. Cancer encompasses a multitude of different disease and victims of it, with their unique genetics, pose different treatment challenges. The refrain that there is no “silver bullet” against cancer—despite what some patients and friends and family of cancer sufferers might think—remains as true as ever.
Asked if the end is in sight, AACR 2016 Program Committee Chairperson Dr. Scott A. Armstrong qualifies his response: “I would say the end is near for finding cures for specific subtypes of cancer. There isn’t likely to ever be a cure. The comparison to infectious disease is a good analogy, I think. Cancer therapy is likely to be the same.”
The main thrust of AACR 2016 will be molecular drivers of cancer. “Immunology has shown dramatic results over the past few years,” Armstrong points out, “especially in metastatic melanoma. Now moving into lung cancer and—in the past two years—leukemia.”
Clinical trials will also be impacted by new discoveries and techniques and refinements of older ones. “We’re now conducting trials where we know what the drug is supposed to target. In the past, when a new drug was tried, perhaps 5 percent would respond. By knowing more about the target beforehand, it’s more likely that patients will respond,” Armstrong states.
Armstrong’s own lab at Memorial Sloan Kettering Cancer Center (MSKCC) in New York is focused on the molecular mechanism of tumor development. As MSKCC notes on its website, the goal of Armstrong’s research program is “to define genetic and epigenetic programs that control the extensive self-renewal properties associated with leukemia and other cancers. This knowledge is then used to develop rational approaches for potential new therapies. Experiments incorporate the use of sophisticated mouse models of leukemia and the characterization of human leukemia cells.”
Epigenetics, Armstrong notes, can lead to cancer development and may represent another group of targets to go after. When asked about his “take-away” points for attending AACR 2016, Armstrong sums up: “Immunotherapy, new techniques and tools such as CRISPR and epigenetics.”
He says he considers it an honor to serve as program chair, noting that previous chairs have made a real impact. Another benefit of being in the driver’s seat for the annual meeting: “It allows you to see progress being made in many areas,” and he stresses that he is grateful to the Program Committee co-chairpersons and Education Committee members for their “dedication, enthusiasm and guidance in shaping a program that will be both enjoyable and educational to attendees, and attract major media attention from around the world.”
This year’s cross-cutting, multidisciplinary program will include an large roster of speakers, hundreds of invited talks and more than 6,000 proffered papers from researchers around the globe. As always, the diversity of the AACR annual meeting program will, the Philadelphia-based organization notes, give presenters a forum to share critical updates in all areas, as well as members of the audience an opportunity to actively participate in discussions with colleagues.
On Saturday, April 16, the full program of educational sessions, methods workshops, meet-the-experts sessions, and award lectures will be presented beginning at 8 a.m. The opening ceremony and the official opening plenary session will take place on Sunday morning, April 17.
“By attending this meeting, you will make fruitful connections, discuss new ideas and hear from the world’s thought leaders in cancer. We feel confident that you will leave the meeting with a sense of energy, inspiration and focus for your work. We look forward to welcoming you to New Orleans in April,” Armstrong states.

A pair of big anniversaries for AACR
During AACR 2016, the American Association for Cancer Research will celebrate two major milestones in publishing. The year 2016 marks the 100th anniversary of the AACR journals publication program, as well as the 75th anniversary of publishing the AACR journal, Cancer Research, which has a long tradition of being the most frequently cited journal in the field. The AACR published the first English-language cancer journal in 1916 and, 100 years later, its publishing program has expanded to include eight high-impact, peer-reviewed scientific journals and an award-winning magazine for cancer survivors, patients and their caregivers.

AACR 2016 Cancer and Biomedical Research Career Fair
Saturday, April 16, 2016
9:30 a.m. to 3 p.m.
Scientists at all levels are invited to attend the AACR Career Fair during the annual meeting in New Orleans. The fair will allow job seekers to connect with employers from academia, government and industry. Representatives from prospective employers will be available to interview job seekers.
Future AACR Annual Meetings​
April 1-5, 2017
Washington, D.C.
April 14-18, 2018
Plenary Sessions
Opening Plenary: Breakthroughs in Cancer Research—Genomics, Epigenetics and Immunomodulation
Sunday, April 17
9:30 a.m. to noon
Cancer genomics: A translational future
Elaine R. Mardis, Washington University School of Medicine, Saint Louis, Mo.
Targeting epigenomic dependencies in cancer
James E. Bradner, Novartis, Cambridge, Mass.
Genome editing using CRISPR-Cas systems
Feng Zhang, Massachusetts Institute of Technology, Cambridge, MA
T cell recognition of human cancer
Ton Schumacher, Netherlands Cancer Institute, Amsterdam, The Netherlands
Stem cells and cancer
Elaine Fuchs, Howard Hughes Medical Institute/Rockefeller University, New York
Metabolic Reprogramming in Cancer
Monday, April 18
8:15 a.m. to 10:15 a.m.
Tumorigenesis is dependent on the reprogramming of cellular metabolism as a direct consequence of oncogenic mutations. An emerging feature of cancer cell metabolism is the ability to acquire necessary nutrients to both maintain viability and build new biomass. The alterations in intracellular and extracellular metabolites that can accompany cancer-associated metabolic reprogramming have profound effects on gene expression, cellular differentiation and the tumor microenvironment. Cancer-associated metabolic changes can be grouped into several distinct hallmark features: (1) deregulated uptake of glucose and amino acids, (2) use of opportunistic modes of nutrient acquisition, (3) use of glycolysis/TCA cycle intermediates for biosynthesis and NADPH production, (4) increased demand for nitrogen, (5) alterations in metabolite-driven gene regulation and (6) metabolic interactions with the microenvironment. How oncogenic mutations reprogram nutrient utilization and how cancer cells sense the adequacy of their supply of anabolic precursors will be discussed. Therapeutic exploitation of these insights will be considered.
Isogenic tumors can utilize heterogeneous mechanisms of nutrient uptake
Craig B. Thompson, Memorial Sloan Kettering Cancer Center, New York
Transcriptional regulation by the MAX-like protein MLX is required for adaptive metabolic responses in development and tumorigenesis
Robert N. Eisenman, Fred Hutchinson Cancer Research Center, Seattle
Targeted inhibition of IDHm in cancer
Katharine Yen, Agios Pharmaceuticals Inc., Cambridge, Mass.
Nutrient sensing pathways in cancer
David M. Sabatini. MIT Whitehead Institute for Biomedical Research, Cambridge, Mass.
Tumor Heterogeneity, Clonal Evolution, and Therapeutic Response
Tuesday, April 19
8:15 a.m. to 10:15 a.m.
Technological advances have revealed complex subclonal architectures of human tumors manifested as genetic and epigenetic intratumor heterogeneity that is dynamic over time and space. Cancer genome instability contributes to variation between single cells in a tumor, providing the substrate for Darwinian selection, fueling intratumor heterogeneity. In this plenary session, speakers will discuss recent advances in our understanding of tumor heterogeneity, from the single cell level and the dependencies of cancer subclones, through to the dynamic nature of the disease over time and space and the impact of selection of low frequency subclones upon therapeutic response. Future approaches and therapeutic strategies will be discussed in light of cancer evolution and tumor heterogeneity focused on improving clinical outcomes.
Tracking Cancer Evolution through Therapy (TRACERx): Implications for immune targeting and surveillance
Charles Swanton. Cancer Research UK London Research Institute, London
The AML genome(s)
Timothy J. Ley, Washington University School of Medicine, St. Louis, Mo.
Dissecting the complex ecosystem of malignant tumors with single cell RNA-Seq
Aviv Regev, Massachusetts Institute of Technology, Cambridge, Mass.
The evolution of cancer in response to targeted therapies
Jeffrey A. Engelman, Massachusetts General Hospital, Boston
Detection and Monitoring of Pre-Malignant Disease and Therapeutic Response
Wednesday, April 20
8:00 a.m. to 10:00 a.m.
This session will summarize the expanding utility of “liquid biopsies” to support patient care. As the sensitivity of circulating tumor DNA (ctDNA) analysis increases, the opportunity for early detection of cancers with a blood test will be explored. Serial analysis of ctDNA to monitor tumor evolution, response and resistance to targeted therapies will be discussed with colorectal cancer the exemplar, a disease where repeat tumor biopsy is challenging. The technical hurdles of circulating tumor cell (CTC) analysis are higher than for ctDNA. Nevertheless, CTCs can provide DNA, RNA and protein data to interrogate the biology of disseminating disease. Focusing on lung cancer, the expansion of CTCs in vivo as CTC-derived patient explant models (CDX) will be outlined together with their use as models of progressive disease (where tumor biopsy is rarely obtained) that can facilitate drug development. The session will conclude with an examination of clonal evolution of myeloid malignancies.
Liquid biopsies and the early diagnosis of cancer
Luis A. Diaz, Johns Hopkins Kimmel Comprehensive Cancer Center, Baltimore, Md.
Heterogeneity, drug resistance and clonal evolution in colorectal cancers
Alberto Bardelli, University of Turin, Candiolo, Italy
Developing circulating tumor cell-derived explant models (CDX)
Caroline Dive, CRUK Manchester Institute, Manchester, U.K.
Clonal hematopoiesis of indeterminate potential
Benjamin Ebert. Brigham & Women’s Hospital, Boston
AACR Annual Meeting 2016 Highlights: Vision for the Future
Wednesday, April 20
12:15 p.m. to 1:45 p.m.
Basic Science
Scott A. Armstrong, Memorial Sloan Kettering Cancer Center, New York
José Baselga, Memorial Sloan Kettering Cancer Center, New York
Early Detection and Prevention Research
Elaine R. Mardis, Washington University School of Medicine, Saint Louis, Mo.
Wrap-up and Vision for the Future
Nancy E. Davidson, University of Pittsburgh Cancer Institute, Pittsburgh
Major Sessions
Developmental Pathways    
Sunday, April 17
2:15 p.m. to 4:00 p.m.
Despite the complexity of cancer, it is now well established that tumorigenesis subverts the same cellular and molecular mechanisms that are employed in cell differentiation and tissue morphogenesis during normal development. A mechanistic understanding of developmental mechanisms and how such mechanisms are altered during tumor initiation and progression holds great promise for developing the next generation of anticancer agents. This major symposium brings together investigators in developmental biology and cancer to discuss their latest research on signaling pathways regulating tissue growth and stem cell renewal in normal development, regeneration and tumorigenesis. They will also discuss efforts aimed at pharmacological intervention of these developmental pathways as cancer therapeutics.
Stem cells and signaling pathways in regeneration and malignancy
Philip A. Beachy, Stanford University, Stanford, Calif.
Targeting stem cell pathways in human cancer
Ruggero De Maria and Marcello Maugeri-Saccà, Regina Elena National Cancer Institute Roma, Rome
The Hippo signaling pathway in organ size control and tumorigenesis
Duojia D. J. Pan, Johns Hopkins Medical Institutes, Baltimore, Md.
Epigenetics and Signaling in Cancer
Sunday, April 17
2:15 p.m. to 4:00 p.m.
Oncogenic signaling pathways and epigenetic programs are both deregulated in human cancer. However, we are now beginning to appreciate the bidirectional convergence of cell signaling and epigenetic remodeling. This session will focus on the expanding evidence of cross talk between oncogenic signaling and epigenetic pathways, the cooperativity of defects in these pathways in human cancer and how we may exploit current insights to develop mechanism-based combination therapies.
Convergence of signaling activation and epigenetic dysregulation in myeloid malignancies
Ross L. Levine, Memorial Sloan Kettering Cancer Center, New York
Co-targeting epigenetic regulators and oncogenic signaling pathways in cancer
Karen Cichowski, Brigham & Women’s Hospital, Boston, Mass.
Epigenetic and kinase crosstalk in solid tumors
Ramon E. Parsons, Icahn School of Medicine at Mount Sinai, New York
Meet-the-Expert Sessions
Immune checkpoint blockade in cancer therapy
James P. Allison, UT MD Anderson Cancer Center, Houston, Texas
The history of this new approach to cancer therapy, its mechanism, and future developments will be discussed, as will the prospects for cures.
Linking genes, environment, and cancer: Lessons from the mouse
Allan Balmain, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco
Human cancers arise due to a complex combination of factors, including inherited polymorphisms in cancer susceptibility genes and exposure to environmental agents that cause genetic or epigenetic changes in the genome. Crosses between different mouse strains can recapitulate the germline genetic heterogeneity in human populations, and environmental exposure to carcinogens, in contrast to genetically engineered mouse cancer models, can induce the complex point mutation signatures and genomic aberrations that are found in human cancers. Both features contribute to the heterogeneity at the cellular and genetic levels that characterizes human cancers, and contributes to resistance to targeted therapies. These integrated model systems provide a promising route to the identification of the critical interacting components of signaling networks that are linked to cancer. Chemically induced tumors that have many point mutations provide a platform for the testing of novel approaches to combinatorial immunotherapy which is dependent on expression of novel neo-antigens in tumors.
Real-time Metabolic and Molecular Imaging of Cancer Systems by Hyperpolarization
Pratip Bhattacharya, MD Anderson Center, Houston, Texas
Imaging aberrant metabolism in cancer systems and metabolic responses to therapy by hyperpolarization are emerging areas of current interest. Hyperpolarization allows for over 10,000-fold sensitivity enhancement relative to conventional MRI and is a non-toxic, non-radioactive method for assessing tissue metabolism and other physiologic properties. After hyperpolarization, the signal enhancement can be retained on the metabolites of the hyperpolarized molecules for several minutes depending upon the relaxation times. Several hyperpolarized (13C and 15N labeled) compounds are employed to image various other metabolic pathways with varying degrees of success. In the past few years, Bhattacharya’s laboratory has developed the direct in-vivo imaging modality of hyperpolarized 29Si nuclei in silicon microparticles and nanoparticles using MRI. Unlike other nuclei (13C, 15N) where hyperpolarized signal lasts for only one to two minutes, the 29Si hyperpolarized signal has a long characteristic decay time of ~50 minutes, and polarization times are unaffected by surface functionalization or the in-vivo environment, thereby allowing a long (>1 hour) time window for diagnostic imaging. Real-time imaging with hyperpolarization may open up the possibility of a new imaging modality wherein the local status of the tumor be potentially interrogated on a time scale of minutes to hours with high specificity and sensitivity by MRI.
Recent Advances in Diagnostics and Therapeutics Research
Hormone Receptors and Breast Cancer
Sunday, April 17
2:15 p.m. to 4:00 p.m.
Hormone receptors are central mediators of breast cancer phenotypes. The basis for this lies in part with their ability to control cellular programs, such as proliferation or motility specifically in mammary-derived cells. This feature has contributed to making them highly effective therapeutic targets due to a potential for wide therapeutic index. This session will discuss how new findings on somatic mutational events, intrinsic expression and activation of different nuclear receptors and various chromatin states all influence breast cancer dependence on hormone receptors. The impact of these findings on the sensitivity of breast tumors to hormonal therapies in the clinic will be further highlighted. The complexities in how these lineage-specific drivers regulate breast cancer behavior and therapy are likely to prove more broadly applicable to other cancer types and drivers.
Mutational landscape of hormone-independent breast cancer
Sarat Chandarlapaty, Memorial Sloan Kettering Cancer Center, New York
Activation and crosstalk among nuclear receptors in breast cancer
Suzanne D. Conzen. University of Chicago, Chicago
Epigenetics of hormone receptor action in breast cancer
Mathieu Lupien, University of Toronto Ontario Cancer Institute, Toronto, Ontario
Realizing Precision Medicine in Pediatric Oncology
Monday, April 18
10:30 a.m. to 12:15 p.m.
Recent advances in next-generation sequencing technologies make it possible to screen human cancers at diagnosis and relapse in a timely manner that can identify targetable genetic alterations. This session will focus on how these technologies are being harnessed in pediatric cancer in order to inform clinical decisions about therapeutic interventions. Dr. Yael Mosse will discuss how one can achieve the preclinical justification required to move combination therapies into the clinic using neuroblastoma as a model. Dr. Donald Parsons will present data regarding the diagnostic yield of integrated genomic sequencing (including DNA and RNA-based analysis of tumor and germline samples) for solid tumor patients at Texas Children’s Cancer Center and discuss the implications for design of prospective precision oncology trials such as the NCI Pediatric MATCH study. Finally, Dr. Mignon Loh will present how the Acute Lymphoblastic Leukemia Committee of the Children’s Oncology Group is acting upon targetable lesions in a series of clinical trials that will overlay signal transduction inhibitors with conventional chemotherapy for eligible patients.
Improving outcomes for patients with neuroblastoma via rational development of novel therapeutic strategies
Yael P. Mosse, Children’s Hospital of Philadelphia
Exomes and beyond: Clinical sequencing for pediatric solid tumor patients
Donald W. Parsons, Baylor College of Medicine Cancer Center, Houston, Texas
Translating genomic discoveries into therapy for acute lymphoblastic leukemia
Mignon L. Loh, University of California, San Francisco
Drugging the Cell Cycle
Monday, April 18
10:30 a.m. to 12:15 p.m.
While many effective, empirically discovered cancer therapies kill cancer cells in a cell cycle-dependent manner, targeted agents against specific components of the cell cycle machinery have been less successful. This has begun to change: In 2015, we had the first approval of a CDK inhibitor, and several promising agents engaging cell cycle targets are in advanced development in a number of cancer types. This session will discuss advanced ongoing work to “drug the cell cycle” with a focus on cell cycle dependent effects of two novel inhibitors (Wee1 and CDK4/6), as well as novel activities of anti-microtubule drugs.
Mechanisms of action of the CDK4 and CDK6 inhibitor abemaciclib: Single-agent and combination activities in preclinical models for human cancer
Richard Beckmann, Eli Lilly and Co., Indianapolis, Ind.
Recent Advances in Organ Site Research
Multiple Myeloma
Sunday, April 17
2:15 p.m. to 4:00 p.m.
There have been rapid advances in our understanding of the genomics underlying the heterogeneity, pathogenesis, and treatment of multiple myeloma. Dr. Faith Davies will update the clinical impact of genomic profiling on diagnosis, prognosis and treatment. Based upon current understanding of the biology of myeloma, Dr. Sagar Lonial will describe novel state-of-the-art therapies for newly diagnosed patients, including both induction and maintenance treatment strategies. Finally, Dr. Kenneth Anderson will describe current therapies for relapsed and refractory myeloma, as well as future targeted and immune single agent and combination therapies. Already patient outcome has been markedly improved, and further progress will derive from advances in all three areas.
The impact of genomics on diagnosis, prognosis and treatment of myeloma
Faith Davies, University of Arkansas for Medical Sciences, Little Rock, Ark.
The importance of plasma cell biology in treating newly diagnosed multiple myeloma
Sagar Lonial, Emory University Winship Cancer Institute, Atlanta, Ga.
Treatment of relapsed myeloma with novel targeted and immune therapies
Kenneth C. Anderson, Dana-Farber Cancer Institute, Boston
New Actionable Targets in Malignancies of the Upper Aerodigestive Tract
Sunday, April 17
2:15 p.m. to 4:00 p.m.
Large-scale genomic sequencing and comprehensive molecular profiling efforts in malignancies of the upper aerodigestive tract—including squamous cell cancer of the head and neck (SCCHN), esophageal and nasopharyngeal (NPC) cancers—have revealed potentially actionable therapeutic targets. Viral infections are implicated in the etiology of some of these cancers, such as the human papillomavirus in SCCHN and Epstein-Barr virus in NPC. Besides offering the prospects of matching genotypes to specific molecularly targeted agents, the molecular landscapes of these malignancies may also provide insights into their immunogenicity and potential sensitivity to immunotherapy.
Whole exome sequencing study of nasopharyngeal and esophageal cancers
H. Phillip Koeffler, Cedars-Sinai Medical Center, Los Angeles
Comprehensive molecular profiling datasets in head and neck squamous cell cancer
Jennifer Rubin Grandis, University of California, San Francisco
What are actionable targets in the management of head and neck squamous cell and nasopharyngeal cancers?
Brigette B. Ma, Chinese University of Hong Kong
Recent Advances in Prevention Research
Global Cancer Prevention
Sunday, April 17
2:15 p.m. to 4:00 p.m.
Cancer prevention is a major component of cancer control to reduce the cancer burden and the wide disparities in cancer control globally. The real world experiences in implementing and scaling up of specific interventions such as tobacco control, hepatitis B vaccination, human papillomavirus vaccination and screening (among others) and their impact on disease burden will be reviewed. Cervical cancer is the most common or the second most common cancer among women in many low-and middle-income countries (LMICs) and is an eminently preventable disease. The recent innovations in early detection and treatment of precancerous lesions and preventing cervical cancer will be reviewed. The challenges in scaling up of currently available cervical cancer interventions in health services will be reviewed. Esophageal cancer is a lethal cancer that contributes to substantial disease burden in many LMICs with poor survival prospects following treatment. The recent experiences in its prevention in People’s Republic of China will be reviewed in the context of global esophageal cancer prevention
Global experiences in implementing cancer prevention interventions in low- and middle-income countries (LMICs)
Rengaswamy Sankaranarayanan, International Agency for Research on Cancer, Lyon, France
Innovative approaches to prevent and treat cervical cancer globally
Kathleen Schmeler, UT MD Anderson Cancer Center, Houston, Texas
Esophageal cancer prevention in China
You-lin Qiao, Chinese Academy of Medical Sciences, Beijing
HPV and Cancer
Monday, April 18
1:00 p.m. to 2:45 p.m.
Recently there has been important progress in the prevention, screening and treatment of HPV-associated cancers, which include cervical cancer, several other types of anogenital cancer and oropharygeal cancer. Most of these improvements are the result of precision medicine, as they are based on the recognition of HPV as the etiologic agent of these cancers. The presentations in this session will highlight recent key achievements in this area and discuss the potential of ongoing research to result in additional practice-changing advances.
HPV vaccines: Recent advances and the potential for further progress
Douglas R. Lowy, National Cancer Institute, Bethesda, Md.
The future of cervical screening in the vaccine era: HPV testing, typing and triage
Mark W. Schiffman, National Cancer Institute’s Division of Cancer Epidemiology and Genetics, Rockville, Md.
HPV and the host genome
Maura L. Gillison, Ohio State University Comprehensive Cancer Center, Columbus, Ohio

NextGen Stars
Applications for AACR 2016’s NextGen Stars program closed on Oct. 30, 2015—and, as of publication time of this issue, the names of the chosen individuals had not been released publicly. But below you can get a sense of the kinds of things you might see from this year’s “stars” by seeing the lineup from AACR 2015.
The NextGen Stars program provides an 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.
Six applicants, give or take, are chosen to give a talk, regardless of the number of applications received. Selected talks are added to existing Major Symposia and Recent Advances sessions, based on the subject matter of the abstract. Most talks are 15 minutes in length plus five minutes for discussion, but the assigned length of the talk may vary depending on the session.           
NextGen Stars of AACR 2015:
Christopher E. Barbieri, Weill Cornell Medical College of Cornell University, New York
SPOP mutation is associated with genomic instability in prostate cancer
Presented in a Recent Advances in Diagnostics and Therapeutics Research session on Exploiting DNA Repair Deficiencies in Cancer
Katherine B. Chiappinelli, Johns Hopkins School of Medicine, Baltimore, Md.
Immunomodulatory and tumor cell killing effects of the demethylating agent 5-azacytidine in ovarian cancer
Presented in a Major Symposium on Epigenetic Mechanisms in Cancer Risk
Ryan B. Corcoran, Massachusetts General Hospital Cancer Center, Boston
Clinical acquired resistance to RAF inhibitor combinations in BRAF mutant colorectal cancer through MAPK pathway alterations
Presented in a Major Symposium on Mechanisms of Resistance: From Signaling Pathways to Stem Cells
Courtney Hodges, Howard Hughes Medical Institute and Stanford University School of Medicine, Stanford, Calif.
Chromatin accessibility underlies the tumor-suppression role of BAF (mSWI/SNF) complexes in many malignancies
Presented in a Recent Advances in Diagnostics and Therapeutics Research session on DNA Repair Pathways in Cancer: Basic Biology and Clinical Utility
Hongbo Pang, Sanford-Burnham Medical Research Institute, La Jolla, Calif.
A novel endocytic and intercellular transport pathway for drug delivery across blood vessels and into nutrient-deprived tumor cells
Presented in a Recent Advances in Diagnostics and Therapeutics Research session on Novel Delivery Systems and/or Formulations in Cancer Treatment
Rushika M. Perera, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston
Transcriptional mechanisms for autophagy regulation and metabolic reprogramming in pancreatic cancer
Presented in a Recent Advances in Organ Site Research session on Pancreatic Cancer in 2015: An Integrated View of a Complex Disease
Catherine C. Smith, University of California, San Francisco
Polyclonal and heterogeneous resistance to targeted therapy in leukemia
Presented in a Major Symposium on Targeted Therapies in Hematologic Malignancies
Surojit Sur, Ludwig Center at the Johns Hopkins Kimmel Cancer Center, Baltimore, Md.
The Trojan Horse Strategy: Packaging chemotherapeutics can help alleviate toxicity
Presented in a Major Symposium on Applying Systems Biology in the Oncology Clinic
AACR recognizes World Cancer Day
PHILADELPHIA – “On this World Cancer Day, we are proud to join people across the globe in raising public understanding of cancer and the importance of cancer research to conquering cancer and improving public health,” said AACR CEO Margaret Foti as her organization recognized World Cancer Day 2016. “The past several decades have seen significant successes in the United States and other countries in preventing and treating a number of types of cancer, but the global burden of cancer remains immense.
“In 2015, 8.9 million people are estimated to have died from cancer worldwide, almost half of them prematurely from cancers that could have been prevented, and estimates show that this number is likely to rise over the next two decades to 14.6 million per year,” she continued. “Low- and middle-income countries (LMICs) in Africa, Asia, and South America are disproportionally affected, accounting for 70 percent of the world’s cancer deaths. We must commit to working together internationally if we are to reduce the death and morbidity due to this insidious disease worldwide.”
“The AACR is a leader in the global effort to lessen the scourge of cancer by connecting the greatest minds in cancer research through new international collaborations and longstanding partnerships with other cancer organizations. The AACR’s nearly 10,000 international members span 104 countries and territories, and our offices in Shanghai and Toronto are increasingly in a position to bring educational opportunities to more cancer researchers than ever before,” she concluded. “It is only by fostering global sharing of ideas and data that we can bring innovative interventions and proven treatments to people around the world.”
Held annually on Feb. 4, World Cancer Day is an international initiative of the Union for International Cancer Control (UICC) that aims to raise awareness about the global cancer burden; empower individuals with information that will help them take a positive and proactive approach to the fight against cancer; and encourage governments to make cancer research, screening and treatment national priorities. The AACR is an active member of the UICC, an organization that brings together the world’s major cancer societies, ministries of health, research institutes, and patient groups to accelerate the fight against cancer.
A look at life-sciences tools and diagnostics in oncology
BOSTON—Leerink Partners analysts Dan Leonard, Kevin Chen and Michael Sarcone had some thoughts about life-sciences tools and diagnostics in the cancer market by writing on Feb. 12, in part, “Much more work to do in cancer biomarkers; play the picks and shovels.”
Their bottom line, following a conference earlier that week focused on cancer genomics as well as insights coming out of Leerink’s own Biomarkers in Oncology panel was: “We consider a conservative approach the best way for investors to capitalize on the growing interest of novel biomarkers in oncology. For now, we believe investors will be best served sticking with the life-science tools companies, those offering picks and shovels to the biotech firms mining for gold in cancer therapeutics. Pure diagnostics business models are trickier, face several uncertainties that complicate the secular trend, and must be evaluated on a case by case basis.”
Looking at cancer research in the political spotlight, they added: “We think cancer research right now enjoys as favorable a political position as we’ve seen in the last 15 years, punctuated by the announcement of a moonshot program in the most recent State of the Union address. Our conversations suggest single-cell analysis methods in oncology research will play a prominent role. Increased funding should boost the fortunes of research tools companies, and is consistent with our view that the positives outweigh the negatives for this group.”
However, they note that while much has been accomplished, many challenges remain and “We’re struck [that] the conversations we had over the past week are the same we could have had (and did have) two years ago. In targeted therapy, where therapeutic decisions are dictated by the presence or absence of gene marker, we continue to see the community debate the relevant biology for testing as well as the clinical utility of testing. Both questions contribute to what has been a challenging reimbursement environment for these tests. The immuno-therapeutic biomarker landscape remains nascent and feedback on the most prominent biomarker (PD-L1 expression) is mixed. Assessment of additional markers remains early days.”
The analysts also point out that tumor profiling questions remain, such as determining what is the relevant biology and how practically useful are such tests. Access to clinical trials the biggest barrier, they maintain.
“We still see debate over tumor profiling panel mechanics—e.g., panel size (i.e., number of genes), tumor/normal, tumor heterogeneity, tumor dynamics, DNA vs. RNA, tissue vs. liquid, etc. Variant categorization remains non-standardized. While the distribution of variants associated with any given cancer has a long tail, the practical relevance of the tail is uncertain. Broad tumor profiling panels are most useful as clinical trial funneling tools, but lack of practical access to clinical trials is a big barrier.”
They believe only about 3 percent of metastatic cancer patients are enrolled in clinical trials in the United States. Efforts at academic medical centers to create tent studies, which provide testing and back office support for clinical trials at disperse locations, could also help ameliorate the problem of access, though such efforts are still in the very early stages, they note.

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