Dr. Hansel’s research focuses on invasive mechanisms in bladder cancer and application of these findings to the identification of new variants of bladder cancer and modifications to bladder cancer staging criteria. Overall, she has presented her research nationally and internationally, and her work has appeared in more than 130 peer-reviewed publications and testicular cancer. Dr. Hansel received her undergraduate degree in Biology from the Johns Hopkins University and her M.D., Ph.D. degree from the Johns Hopkins School of Medicine.
Dr. Engman is a physician-scientist with clinical expertise in molecular genetic pathology and research interests in emerging infectious diseases and cancer. He has dedicated much of his professional career to the mentoring of scientists, physicians and physician-scientists and directed the Northwestern University MD-PhD Program for nearly twenty years. Dr. Engman served as President of the National Association of MD-PhD Programs and Chair of the MD-PhD Section of the Association of American Medical Colleges. He was voted Mentor of the Year by the faculty of the Northwestern University Feinberg School of Medicine in 2015 and served as Chairman of the Department of Pathology at Cedars-Sinai from 2016 to 2020.
Dr. Chen’s goal is to figure out how myeloid cells are triggered to infiltrate into the Glioblastoma (GBM) tumor microenvironment by glioma cells under specific genetic backgrounds (e.g., PTEN mutation and deletion), and, in turn, how they affect glioma cell biology and induce immunosuppression. Based on these mechanistic studies, he aims to develop novel immunotherapy strategies for GBM.
The purpose of Dr. Cho’s study is to identify the short- and long-term changes in stress, health behaviors, and quality of life and their associations in the transition from active treatment to survivorship. Young adult cancer survivors and their partners will be asked to complete a daily diary survey for 7 consecutive days (‘a burst’) 9 times over 2 years, with the bursts spaced 3 months apart.
Dr. Green is dual board-certified in both pediatric hematology-oncology and infectious diseases. She is an attending physician on the immunocompromised infectious diseases team at St. Louis Children’s Hospital and Assistant Professor in the Department of Pediatrics at Washington University School of Medicine. She is on the Core Leadership Council of the Center for Genome Integrity at Siteman Cancer Center.
2022 DAPER Awardee
Dr. Gryder’s laboratory studies the 3D architecture, composition, and function of long-range enhancers driving cancer gene expression programs. From this vantage point, the Gryder lab is developing new molecular strategies to control and collapse nuclear subcompartments called super-clusters, also known as transcriptional condensates.
Dr. Jang’s research group develops innovative biomaterials and biotechnologies to solve medical problems, especially cancer metastasis in bone. They create an immune-integrated cancer metastasis in bone modeling platform to understand underlying pathological mechanisms and engineer novel immunomodulatory therapies to defeat cancer.
Dr. Jackson is responsible for the operations of the Conrad Prebys Center for Chemical Genomics, a 55-person, multidisciplinary drug discovery enterprise, which has all the capabilities needed for small molecule drug discovery and drug repositioning. Prior to joining SBP, he spent 15 years at Johnson & Johnson developing a track record for research and development as he rose through the ranks from Vice President of Discovery to President of R&D at ALZA Corporation.
Dr. Laurencin is the first surgeon in history elected to all four National Academies: the National Academy of Sciences, the National Academy of Engineering, the National Academy of Medicine, and the National Academy of Inventors. The founder of the field of regenerative engineering, he received the National Medal of Technology and Innovation from President Barack Obama in ceremonies at the White House, the nation’s highest honor for technological achievement. Laurencin received the 2021 Spingarn Medal from the NAACP.
Dr. Rowe’s research is focused on the biology of normal and diseased blood stem cells. He is interested in the mechanisms underlying developmental differences in young and old blood stem cells and how these are perturbed in diseases such as bone marrow failure and leukemia.
2022 DAPER Awardee
Dr. Sethi’s goal is to combine clinical observations and patient-derived data with rigorous basic science investigation to yield opportunities for impactful translational advances. He is committed to defining the mechanisms underlying gastrointestinal cancers with the hope that such insight will translate into new prevention and treatment methods.
2022 DAPER Awardee
The primary goal of Dr. Xue’s research group is to create chemical tools that enable a deeper understanding and effective treatments of human diseases, such as cancer. He takes a convergent approach and innovate through the interdisciplinary sciences involving bioanalytical chemistry, chemical biology, organic chemistry, multivariate statistics, and cancer biology.
2022 DAPER Awardee
Dr. Kuhn is a physicist and educator with a career long commitment in personalized medicine and individualized cancer patient care with a focus on the redesign of cancer care that eliminates uncertainty in treatment choices and outcomes. He has a history of developing disruptive technologies that solve real-world scientific and healthcare problems. He has significant experience in managing large scale research collaborations and interdisciplinary research teams at the interface of physics, life science and medicine. As the founder and director of the Scripps Physics Oncology Center, an NCI supported signature initiative, his research over the past 12 years has focused on the understanding of the fluid phase of solid tumors. At USC this enterprise is known as Convergent Science Institute in Cancer (CSI-Cancer). The results are both advancing cancer care through better understanding of the metastatic process in patients and through the translation of scientific results to clinically useful products. The underlying technology of the center is now being tested in over three thousand patients in the research setting as well as being commercially developed by Epic Sciences. His laboratory is now integrating patient, model system, and high-content single cell genomics data to translate clinically observed correlations into a mechanistic understanding of the physical and biological underpinnings of cancer dynamics to modify outcomes for the diagnosis, prognosis, and therapy management of ovarian, breast, lung, colon, prostate, and other tissue cancers.
Dr. Bertram served 24 years on Active Duty in the U.S. Army as an Internal Medicine and Hematology/Oncology physician, as a medical research Program Manager, and as the Commander of the Walter Reed Army Institute of Research (WRAIR). After retiring as a Colonel, he was selected to lead the Army’s Medical Advanced Development and Acquisitions teams. Dr. Bertram retired from Federal Service in 2018 and now spends half of his time at Wake Forest Institute for Regenerative Medicine leading efforts to bring stem cells into clinical trials and half of his time as a Consultant to BioGenerator helping to bring innovative medical solutions to America’s Service Members and Veterans.
Dr. Cech’s research centers on RNA and RNA-protein complexes. His group studies telomerase, the chromosome end-replicating enzyme that is reactivated in the majority of cancers. They also study how RNA regulates epigenetic silencing. Dr. Cech has been elected to the National Academy of Sciences and the National Academy of Medicine, and he has been awarded the Nobel Prize in Chemistry and the National Medal of Science. He served as president of the Howard Hughes Medical Institute from 2000 to 2009.
Dr. Freedland’s research interests include urological diseases and the role of diet, lifestyle and obesity in prostate cancer development and progression, as well as prostate cancer among racial groups and risk stratification for men with prostate cancer. He is a committed mentor having mentored over 70 mentees and published over 200 publications wherein the mentee was first author.
Dr. Hu is a former military commander of a combat support hospital and served in the army for 30 years. He has more than 20 years of clinical experience in medical oncology and brings this acumen to the bedside. Understanding the rarity of sarcoma cancers, Dr. Hu has collaborated with other national experts on clinical trials and have also been the Principal Investigator of more than 15 clinical studies.
Dr. Randles has 114 U.S. patents and 16 international patents in her name, and counting (mainly in parallel computing), she made international headlines in 2015 for creating the first three-dimensional simulation of blood flow through the human body. Her research in biomedical simulation and high-performance computing focuses on the development of new computational tools that we use to provide insight into the localization and development of human diseases ranging from atherosclerosis to cancer.
Dr. Liphardt’s scientific training is in single-molecule biophysics and thermodynamics of small systems. The focus of his research is to determine how biological systems function. Systems under investigation range from the self-organization of receptors in membranes, the transport of cargos through biological pores, and the control of the DNA loopscape in the nucleus. He co-founded CancerBase, where patients can share medical data and learn from one another.
Dr. Krunic is a dynamic leader with more than 20 years of experience in the global pharmaceutical and diagnostic industries. In her current role at Novartis, she collaborates with strategic external partners and internal teams to identify, evaluate and implement diagnostic solutions for clinical biomarkers supporting development and commercial launch of innovative medicines. She is a core member of the BloodPac Consortium, a board observer at Freenome, and member of the American Society for Clinical Oncology.
Dr. Tai’s research uses MEMS/NEMS technologies such as micromotors, microphones, neural chips, micro relays, micro power generators, micro valves, micro pumps, etc. for medical applications. He collaborates with physicians and biologists across the nation to develop integrated implants for cortical, retinal, and spinal applications. Micro implant devices include spinal neural stimulators, ECG implants, retinal prosthetic devices, intraocular lenses, etc.
Dr. Thompson is a Urologic Oncologist with an interest in early detection, prevention, and treatment of prostate and other GU cancers. He has been a member of the Southwest Oncology Group (SWOG) since the 1980’s and chair of the GU Committee since the early 2000’s. He was in the Army at Brooke Army Medical Center and served as Chair of Urology and Cancer Center Director at the University of Texas Health Science Center. Dr. Thompson joined CHRISTUS Santa Rosa, as Hospital CEO and later with the two System Foundations.
Dr. Page’s research interests have recently been focused on a ‘One Medicine’ approach to cancer. He has served as PI of the Golden Retriever Lifetime Study since 2008 (GRLS) and has led national efforts to bring translational and comparative oncology to a greater audience by developing two National Academy of Science, Engineering and Medicine workshops and coordination of national research consortia for comparative cancer research. He is the 2019 recipient of the AVMA/AKC Career Achievement Award in Canine Research.
Ms. Scher is a senior strategy and operations executive. She has built successful businesses in multiple healthcare sectors including senior care, academic medical centers, wellness, healthcare information and physician offices serving as the organization’s chief operating officer (COO), chief strategy officer (CSO), lead acquisitions executive and chief administrative officer (CAO). Ms. Scher provides guidance on public/private partnerships to enhance strategic missions.
Ms. Lai is a computer scientist, with decades of experience building complex computing infrastructure and machine-learning platforms at a global scale, including for regulated industries such as health science and financial systems. She was previously CTO of GRAIL, where she led the software and bioinformatics team to amass the largest clinical trial data set in oncology, and create a machine-learning platform with bespoke algorithms to detect cancer signals within tumor-derived cell-free nucleic acids in blood. She was previously CTO of GRAIL and spent over a decade at Google, where she was VP of Engineering.
Dr. Spetzler is focused on the development of clinical assays to aid in the creation of precision medicine strategies for individual cancer patients, as well as noninvasive technologies to identify and predict early-stage cancer. He developed multiplexed nanotechnologies for single molecule detection of nucleic acid and protein targets. Dr. Spetzler also developed novel methods of using DNA to create biological computers to solve NP-complete optimization problems and built a novel optical detection system capable of measuring single molecule protein conformational changes with microsecond time resolution.
Dr. Bass is a physician-scientist who has focused on the genomics of gastric and esophageal cancers, followed by defining mechanisms of key genomic aberrations in in vitro and in vivo models. Recently, he moved his research group to Columbia University to serve as a Founding Director of the Center for Precision Cancer Medicine.
Dr. Baas represents the patient voice as one of the four founding editors of the scientific journal Convergent Science Physical Oncology, which focuses on how experimental and theoretical science contributes to a better understanding of cancer complexity and to the development of more effective diagnostic and treatment strategies. She is an advocate reviewer for the DoD Congressionally Directed Medical Research Program, PCORI and Komen.
Dr. Lesniak’s clinical and research interests focus on neurosurgical management of patients with brain and spinal cord tumors. He takes care of patients with both benign as well as malignant cancer of the brain/spinal cord. In addition, part of his practice is devoted to the care of neurovascular patients, including aneurysms and arteriovenous malformations.
Ms. Lewin is an institutional review board community member. She reviews study goals and documents to ensure their clarity and consistency, and the protection of patient rights. As a retired management consultant, she is particularly interested in effective cross functional collaboration and education. Ms. Lewin has authored four books, published numerous articles, and mentored several consultants.
Dr. Link’s research is focused on two general areas: characterizing the regulation of hematopoietic niches in the bone marrow under homeostatic and stress conditions and defining the molecular pathogenesis and treatment of leukemias. Cutting edge genomic, transgenic, and imaging approaches are being used in this research. The Link laboratory emphasizes a collaborative research environment and places a priority on the career development of its trainees.
Dr. Milbury systematically developed a unique program of research evaluating mind-body medicine as well as other behavioral interventions as a supportive care approach for cancer patients and their family caregivers. Her clinical trials are conducted in collaboration with clinicians and scientists representing various disciplines and funded by the National Cancer Institute, the American Cancer Society, and other research foundations.
Mr. Mingle joined the US Navy in 1974 after earning his undergraduate degree in history and political science from Kent State University. He was Executive Officer of the Naval Station in Long Beach when he retired from the US Navy in 1994. Mr. Mingle also serviced as Assistant City Manager for the City of Bellflower in California from 1995 to 2017.
Dr. Peterson’s research focuses on understanding behavioral, psychosocial, and health-related outcomes of persons at increased risk for cancer and other sequelae, across the cancer prevention and survivorship continuum. A cross-cutting theme of her research is the development and evaluation of digital health assessments and interventions for populations at risk for hereditary cancer and cancer survivors. Her research also focuses on psychosocial and behavioral outcomes of genetic testing for hereditary cancer syndromes in cancer survivors and their families, as well as the integration of genomic services into general oncology care.
Dr. Scacheri is a genomicist interested in the role of the epigenome in health and human disease. He is known for his work on transcriptional enhancer elements in human cancer. Dr. Scacheri has published more than 75 peer reviewed papers as well as numerous book chapters, reviews, and perspective articles. He is also deeply committed to graduate student training.
Dr. Sengupta develops novel biotechnologies for clinical translation based on the understanding of underlying biological mechanisms and disease pathology. At a fundamental level, he is currently working on three different themes: (1) the early events of metastasis; (2) understanding the mechanisms (such as phenotypic plasticity) that allow cancer cells to tolerate chemotherapy; and (3) developing next generation therapeutics, including nanomedicines, that can modulate the tumor stromal contexture, including the immune cells.
Dr. Shivdasani’s laboratory investigates the fundamental biology of digestive tract stem cells and cancers, with a focus on epigenetic and transcription factor determinants of organogenesis, cell differentiation, and neoplasia. The overarching goal is to understand, deeply and beyond the mutational paradigm, how normal cells become cancerous and how stem cell and differentiation mechanisms may be leveraged to help reverse the process.
Dr. Wang received his Ph. D. degree from Washington University in St. Louis after obtaining his BS and MS degrees from Shandong University and Dalian Institute of Chemical Physics, Chinese Academy of Sciences, respectively. Dr. Wang’s research involves the use of mass spectrometry, along with synthetic organic chemistry and molecular biology, for investigation about the occurrence and biological consequences of DNA damage as well as for the identification and functional characterizations of nucleic acid- and nucleotide-binding proteins.
Dr. Zon’s laboratory aims to dissect how assaults to the hematopoietic system cause severe diseases such as leukemias, lymphomas, and anemias. They investigate hematopoietic development and disease using chemical screens, genetic screens, and analysis of novel transgenic lines in zebrafish. Dr. Zon is internationally recognized for his pioneering work in stem cell biology and cancer genetics. He also maintains an active research program in the developmental origins of melanoma.
Dr. Blackwell is an expert in metastatic breast cancer who led programs that resulted in numerous groundbreaking regulatory approvals in the cancer field. She has led oncology therapeutic development including IO assets and biomarker development as well as drug development and served on Boards of Directors and Scientific Advisory Boards of Pharma and Biotech companies. Dr. Blackwell’s innovative work in developing non-chemotherapy-based approaches for the treatment of breast cancer led to her inclusion on TIME magazine’s 2013 list of the 100 most influential people in the world.
Dr. Shriver trained in Surgical Oncology at Memorial Sloan-Kettering Cancer Center. He is a renowned researcher with interests in cancer epidemiology, proteogenomics, surgical technique advances, and breast cancer. Dr. Shriver served 34 years on active duty with the Army and deployed four times in support of overseas combat operations.
Dr. Moore is a biomedical informatician with expertise in the development, evaluation, and application of artificial intelligence (AI) algorithms, methods, and software for the analysis of big biomedical and clinical data. His recent work has focused on the development of automated machine learning (AutoML) methods for democratizing AI.
Dr. Lopez works as a Program Administrator of Cancer Navigation, Survivorship and Advocacy at the Cedars-Sinai Cancer, Community Outreach and Engagement team, leading several community-based projects that can improve access and quality of life for patients and their loved ones; and promoting bidirectional research between patients, community, and scientists.
In addition to that, she is also known as a global cancer research advocate. She reviews research protocols, chairs committees, and collaborates with multiple scientists, clinicians, fellow survivor advocates, government entities, small and large nonprofits within the state of CA, nationally and abroad. Dr. Lopez survived breast and thyroid cancers in her early 30s. Since then, her mission became making the road a bit easier for underrepresented cancer groups, especially those who experience cultural and linguistical barriers.
Dr. Kay serves as the Provost Professor of Neurology, Biomedical Engineering and Quantitative Computational Biology and the Director of Convergent Bioscience at USC. He also directs the USC MESH Academy. Dr. Kay leads a large interdisciplinary research hub that merges medicine, engineering and the sciences with the goal of accelerating the discovery of novel therapeutics and diagnostics.
His research lab investigates the molecular basis of circadian rhythms and their relation to cancer therapeutics in humans and also agricultural biotechnology in crop plants. Steve Kay Laboratory – The Keck School of Medicine (usc.edu)
Dr. Van Eyk is an international leader in the area of clinical proteomics and her lab has focused on developing technical pipelines for de novo discovery and larger scale quantitative mass spectrometry methods. This includes multiple reaction monitoring (MRM, also known as SRM) and most recently data independent acquisition. Dr. Van Eyk’s laboratory is well known for the extreme technical quality of the data generated, rigorous quality control with tight %CV while applying these to key clinical questions. The aim is to maximize throughput and reproducibility in order to move targeted and robust discovery methods into large population healthy continuous assessment and clinical grade assays focusing on brain and cardiovascular diseases.
Dr. Venteicher’s lab studies non-canonical mechanisms of tumorigenesis, focusing on brain cancers. We study chromatin architecture, inter- and intra-tumoral heterogeneity, and cellular state using genomics applied to human cancer.
The ultimate objective of Dr. Miller’s work is to develop new strategies for the risk-stratification, prevention, and treatment of MDS and AML, particularly therapy-related disease. His lab seeks to understand how PPM1D influences hematopoietic cells’ susceptibility to malignant transformation and how PPM1D alters the response to cytotoxic agents. From a direct translational therapeutic perspective, their goals are to (1) define classes of currently used treatments that would be most effective in t-MN and most enhanced with concurrent PPM1D inhibition, (2) highlight therapeutic contexts where PPM1D inhibitors would be most efficacious and (3) identify new potential drug targets downstream of PPM1D that mediate transformation and therapy resistance.
Colorectal cancer (CRC) affects 1.5 million patients in the U.S. Immune checkpoint inhibitors (ICIs) are integral parts of treating metastatic and recurrent CRCs with high microsatellite instability (MSI-H). Nonetheless, 60-69% of MSI-H CRC patients do not respond to ICIs. In addition, immune-related adverse events (irAEs) affect 39-71% of patients receiving ICIs and are difficult to predict. Dr. Yu’s CSVCC research goals are to identify the digital pathology profiles indicative of ICI responses via artificial intelligence methods, predict the risk of irAEs, and optimize treatment strategies for CRC patients.
Developing a successful cancer research program that will improve outcomes for cancer patients requires an active understanding of emerging concepts and technologies in cancer research and changing patient needs. Dr. Dedhia expects to develop new approaches to answer research questions, improved grant and manuscript writing skills, multi-institutional collaborations, and a national presence. Similarly, she hopes to contribute her molecular biology and organoid development expertise, clinical perspective, and surgical access to patient tissues in order to support the research of her peers in the CSVCC. Dr. Dedhia hopes to not only develop her own professional network but also strengthen the breadth of other members of the CSVCC by building on the opportunities afforded through the CSVCC.
This project aims to generate novel therapeutic ideas for bladder and colorectal cancers that show resistance to cytotoxic chemotherapy. Dr. Rogala’s focus is on targeting cancers that thrive in nutrient-depleted environments. Surprisingly, despite these cancers theoretically being at a disadvantage, they manage to survive and resist the effects of anti-cancer drugs. His primary aim is to pinpoint specific proteins that are crucial for the survival of these cancers, reveal how these proteins work on the molecular level, and develop experimental drugs to stop them in their tracks
Colorectal cancer (CRC) is a prevalent and highly fatal type of cancer that affects people worldwide. While a small percentage of CRC cases can be attributed to known genetic factors, the majority of cases are influenced by environmental factors that contribute to its development. This emphasizes the significant impact of modifiable behavioral practices that can be adjusted to support efforts in preventing CRC, or even treating existing polyps or tumors. Recently, Dr. Levy’s team has discovered a new molecular pathway through which diets can inhibit tumor growth in the intestine. Specifically, her research demonstrated that ketogenic diets, which are low in carbohydrates and high in dietary fats, have the potential to prevent colorectal cancer development in both animal models and human cancer cells. Her current objective is to delve into the mechanisms responsible for this protective effect, aiming to advance this discovery towards practical applications for patients.
When it is first diagnosed in a patient, the glioblastoma genome is catastrophically altered. Supported by the CSVCC, Dr. Barthel will investigate the role of telomere dysfunction in shaping the cancer genome.
Dr. Largaespada is an authority on mouse genetics, gene modification, and cancer genes. He received his BS in Genetics and Cell Biology from the University of Minnesota, Twin Cities in 1987 and his PhD in Molecular Biology with Dr. Rex Risser at the University of Wisconsin-Madison in 1992. He did a post-doctoral fellowship at the National Cancer Institute working with world-renowned geneticists Dr. Nancy Jenkins and Dr. Neal Copeland, where the Leukemia and Lymphoma Society of America awarded him a post-doctoral fellowship. He joined the faculty of the University of Minnesota in late 1996. Dr. Largaespada currently holds the Hedberg Family/Children’s Cancer Research Fund Chair in Brain Tumor Research. He was awarded the American Cancer Society Research Professor Award in 2013, the highest award given by the ACS.
Dr. Ogino has developed the integrative scientific field of molecular pathological epidemiology (MPE). Dr. Ogino founded the International Molecular Pathological Epidemiology (MPE) Meeting Series (www.mpemeeting.org) in 2013 and has been serving as its Chair/Co-Chair for six past meetings. Dr. Ogino is a leading investigator to study the interactive roles of exposures, genetics, systemic conditions such as obesity, microbiome, and immunity in cancer biology and etiologies. He has conducted multimodal, multi-omic studies using large-scale prospective cohort studies and clinical trials, having discovered the etiological links between certain diets / lifestyle factors and microbiota / immune cell infiltrates in the tumor microenvironment. Recently, Dr. Ogino devotes his research effort to early-onset cancers that have shown increased incidence in recent decades. Those include mostly GI and/or obesity-related early-onset cancer types such as cancers in the colorectum, breast, bone marrow (myeloma), endometrium, esophagus, extrahepatic bile duct, gallbladder, head and neck, kidney, liver, pancreas, and stomach. As one of thought leaders in this particular topic, Dr. Ogino applies integrative research approaches to address this global issue. For his unique transdisciplinary scientific contribution, Dr. Ogino has received numerous awards and honors.
The Ringel Lab is dedicated to studying mechanisms of cancer invasion, metastatic progression, and therapeutic resistance in thyroid cancer. One of the most active thyroid cancer laboratories in the country, the Ringel Lab experts focus on translational discoveries designed to enhance clinical thyroid cancer care through basic science. He has ongoing collaborations with investigators in the OSU Colleges of Medicine, Veterinary Medicine, and Engineering studying mechanisms by which cancer invade and metastasize.
The overarching goal of Dr. Lengner’s research program is to gain an understanding of the molecular mechanisms that govern stem cell potency and how dysregulation of these mechanisms can contribute to disease onset and progression, including oncogenesis. His laboratory employs genetic, genomic, and single-cell analysis approaches in murine systems to address these fundamental questions, and, in parallel, utilizes human induced pluripotent cells and patient samples to translate findings into human systems. Using these approaches they have identified novel pathways underlying the somatic stem cell self-renewal and the ontogeny of hematopoietic and gastrointestinal cancers. These pathways are subsequently being assessed as potential points for therapeutic intervention in cancers and diseases of regenerative failure. They have also begun to unravel the hierarchical structure of the intestinal stem cell compartment with the ultimate goal of understanding how perturbations in this hierarchy contribute to disease states, including cancer, chronic inflammation, and regeneration in response to acute injuries such as ischemia or radiation damage.
Dr. Artandi is an oncologist and cancer biologist whose research work has focused on the role played by the enzyme telomerase in cancer, aging and stem cell function. His work has produced new insights into the origins of cancer, revealing how telomerase endows cells with immortal growth properties and how aspiring cancers circumvent critical bottlenecks encountered during carcinogenesis.