Precancer Atlas to Drive Precision Prevention Trials

Published on Apr 1, 2017in Cancer Research8.38
· DOI :10.1158/0008-5472.CAN-16-2346
Avrum Spira36
Estimated H-index: 36
(BU: Boston University),
Matthew B. Yurgelun14
Estimated H-index: 14
(Harvard University)
+ 17 AuthorsScott M. Lippman91
Estimated H-index: 91
(UCSD: University of California, San Diego)
Cancer development is a complex process driven by inherited and acquired molecular and cellular alterations. Prevention is the holy grail of cancer elimination, but making this a reality will take a fundamental rethinking and deep understanding of premalignant biology. In this Perspective, we propose a national concerted effort to create a Precancer Atlas (PCA), integrating multi-omics and immunity – basic tenets of the neoplastic process. The biology of neoplasia caused by germline mutations has led to paradigm-changing precision prevention efforts, including: tumor testing for mismatch repair (MMR) deficiency in Lynch syndrome establishing a new paradigm, combinatorial chemoprevention efficacy in familial adenomatous polyposis (FAP), signal of benefit from imaging-based early detection research in high-germline risk for pancreatic neoplasia, elucidating early ontogeny in BRCA1 -mutation carriers leading to an international breast cancer prevention trial, and insights into the intricate germline-somatic-immunity interaction landscape. Emerging genetic and pharmacologic (metformin) disruption of mitochondrial (mt) respiration increased autophagy to prevent cancer in a Li-Fraumeni mouse model (biology reproduced in clinical pilot) and revealed profound influences of subtle changes in mt DNA background variation on obesity, aging, and cancer risk. The elaborate communication between the immune system and neoplasia includes an increasingly complex cellular microenvironment and dynamic interactions between host genetics, environmental factors, and microbes in shaping the immune response. Cancer vaccines are in early murine and clinical precancer studies, building on the recent successes of immunotherapy and HPV vaccine immune prevention. Molecular monitoring in Barrett9s esophagus to avoid overdiagnosis/treatment highlights an important PCA theme. Next generation sequencing (NGS) discovered age-related clonal hematopoiesis of indeterminate potential (CHIP). Ultra-deep NGS reports over the past year have redefined the premalignant landscape remarkably identifying tiny clones in the blood of up to 95% of women in their 50s, suggesting that potentially premalignant clones are ubiquitous. Similar data from eyelid skin and peritoneal and uterine lavage fluid provide unprecedented opportunities to dissect the earliest phases of stem/progenitor clonal (and microenvironment) evolution/diversity with new single-cell and liquid biopsy technologies. Cancer mutational signatures reflect exogenous or endogenous processes imprinted over time in precursors. Accelerating the prevention of cancer will require a large-scale, longitudinal effort, leveraging diverse disciplines (from genetics, biochemistry, and immunology to mathematics, computational biology, and engineering), initiatives, technologies, and models in developing an integrated multi-omics and immunity PCA – an immense national resource to interrogate, target, and intercept events that drive oncogenesis. Cancer Res; 77(7); 1510–41. ©2017 AACR .
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Published on Dec 1, 2017in Genome Biology14.03
Simone Ecker9
Estimated H-index: 9
(UCL: University College London),
Lu Chen14
Estimated H-index: 14
(University of Cambridge)
+ 21 AuthorsFrancesco Paolo Casale11
Estimated H-index: 11
(EMBL-EBI: European Bioinformatics Institute)
Background A healthy immune system requires immune cells that adapt rapidly to environmental challenges. This phenotypic plasticity can be mediated by transcriptional and epigenetic variability.
Published on Dec 1, 2017in Respiratory Research3.83
Andre Koper1
Estimated H-index: 1
Leo Zeef28
Estimated H-index: 28
(University of Manchester)
+ 4 AuthorsRichard Booton20
Estimated H-index: 20
Background Preinvasive squamous cell cancer (PSCC) are local transformations of bronchial epithelia that are frequently observed in current or former smokers. Their different grades and sizes suggest a continuum of dysplastic change with increasing severity, which may culminate in invasive squamous cell carcinoma (ISCC). As a consequence of the difficulty in isolating cancerous cells from biopsies, the molecular pathology that underlies their histological variability remains largely unknown.
Published on Dec 1, 2017in Diagnostic Pathology2.53
Ying Chen1
Estimated H-index: 1
(Sichuan University),
He Wang8
Estimated H-index: 8
(Sichuan University)
+ 1 AuthorsPing Shuai1
Estimated H-index: 1
Background This study aimed to assess the role of RNA-dependent adenosine deaminase (ADAR1) in cervical squamous cell carcinoma occurrence and progression.
Published on Oct 1, 2017in Cancer Prevention Research3.87
Ester Borras10
Estimated H-index: 10
(University of Texas MD Anderson Cancer Center),
Kyle Chang29
Estimated H-index: 29
(University of Texas MD Anderson Cancer Center)
+ 9 AuthorsPatrick M. Lynch64
Estimated H-index: 64
(University of Texas MD Anderson Cancer Center)
Lynch syndrome (LS) is a genetic condition secondary to germline alterations in the DNA mismatch repair (MMR) genes with 30% of changes being variants of uncertain significance (VUS). Our aim was to perform an in silico reclassification of VUS from a large single institutional cohort that will help prioritizing functional validation. A total of 54 VUS were detected with 33 (61%) novel variants. We integrated family history, pathology, and genetic information along with supporting evidence from e...
Published on Oct 1, 2017in Gut17.94
Matthew F. Buas9
Estimated H-index: 9
(Fred Hutchinson Cancer Research Center),
Qianchuan He7
Estimated H-index: 7
(Fred Hutchinson Cancer Research Center)
+ 37 AuthorsRebecca C. Fitzgerald19
Estimated H-index: 19
(University of Cambridge)
This work was principally supported by the National Institutes of Health (R21DK099804 to MMM and R01CA136725 to TLV and DCW). Support for studies related to the Oxford data set was granted by the Esophageal Adenocarcinoma GenE Consortia incorporating the ChOPIN project (grant C548/A5675) and Inherited Predisposition of neoplasia analysis of genomic DNA (IPOD) from AspECT and BOSS clinical trials project (grant MGAG1G7R); Cancer Research UK (AspECT, grants C548/A4584 and D9612L00090, and Histolog...
Published on Aug 31, 2017in Oncogene6.63
Judit Zámborszky5
Estimated H-index: 5
(MTA: Hungarian Academy of Sciences),
Bernadett Szikriszt2
Estimated H-index: 2
(MTA: Hungarian Academy of Sciences)
+ 10 AuthorsZoltan Szallasi52
Estimated H-index: 52
Loss of BRCA1 or BRCA2 markedly increases the rate of base substitution mutagenesis and has distinct effects on genomic deletions
Published on Aug 1, 2017in Lancet Oncology35.39
Jennifer Beane15
Estimated H-index: 15
(BU: Boston University),
Joshua D. Campbell12
Estimated H-index: 12
(BU: Boston University)
+ 2 AuthorsAvrum Spira36
Estimated H-index: 36
(BU: Boston University)
Summary Although major advances have been reported in the last decade in the treatment of late-stage cancer with targeted and immune-based therapies, there is a crucial unmet need to develop new approaches to improve the prevention and early detection of cancer. Advances in genomics and computational biology offer unprecedented opportunities to understand the earliest molecular events associated with carcinogenesis, enabling novel strategies to intercept the development of invasive cancers. This...
Published on Aug 1, 2017in Clinical Cancer Research8.91
Janelle B. Pakish3
Estimated H-index: 3
(University of Texas MD Anderson Cancer Center),
Qian Zhang12
Estimated H-index: 12
(University of Texas MD Anderson Cancer Center)
+ 7 AuthorsMelinda S. Yates9
Estimated H-index: 9
(University of Texas MD Anderson Cancer Center)
Purpose: Recent studies show that colorectal tumors with high microsatellite instability (MSI-H) have increased immunogenicity and response to immunotherapy compared with microsatellite-stable (MSS) tumors. It is not yet clear whether MSI-H endometrial cancer may also benefit from these therapies. It is also unknown whether immune response is equivalent in MSI-H endometrial cancer with sporadic or inherited Lynch syndrome origins. Experimental Design: Multiplexed fluorescent IHC was used to comp...
Published on Jul 1, 2017in JAMA Oncology22.42
Raaj S. Mehta11
Estimated H-index: 11
(Harvard University),
Reiko Nishihara34
Estimated H-index: 34
+ 21 AuthorsYohei Masugi20
Estimated H-index: 20
(Harvard University)
Importance Fusobacterium nucleatum appears to play a role in colorectal carcinogenesis through suppression of the hosts’ immune response to tumor. Evidence also suggests that diet influences intestinal F nucleatum. However, the role of F nucleatum in mediating the relationship between diet and the risk of colorectal cancer is unknown. Objective To test the hypothesis that the associations of prudent diets (rich in whole grains and dietary fiber) and Western diets (rich in red and processed meat,...
Published on Jul 1, 2017in Journal of the National Cancer Institute10.21
Joseph Perez-Rogers3
Estimated H-index: 3
(BU: Boston University),
Joseph Gerrein3
Estimated H-index: 3
(BU: Boston University)
+ 11 AuthorsDavid A. Elashoff1
Estimated H-index: 1
(BU: Boston University)
Cited By32
Published on Apr 1, 2019in Trends in Cell Biology16.59
Kunihiko Hinohara14
Estimated H-index: 14
(Harvard University),
Kornelia Polyak81
Estimated H-index: 81
(Harvard University)
Most human tumors are composed of genetically and phenotypically heterogeneous cancer cell populations, which poses a major challenge for the clinical management of cancer patients. Advances of single-cell technologies have allowed the profiling of tumors at unprecedented depth, which, in combination with newly developed computational tools, enable the dissection of tumor evolution with increasing precision. However, our understanding of mechanisms that regulate intratumoral heterogeneity and ou...
Published on Jun 24, 2019in Familial Cancer2.21
Adriana M. Coletta (UofU: University of Utah), Susan K. Peterson23
Estimated H-index: 23
(University of Texas MD Anderson Cancer Center)
+ 11 AuthorsMiguel A. Rodriguez-Bigas55
Estimated H-index: 55
(University of Texas MD Anderson Cancer Center)
Lifestyle factors related to energy balance, such as excess body weight, poor diet, and physical inactivity, are associated with risk of sporadic endometrial cancer (EC) and colorectal cancer (CRC). There are limited data on energy balance-related lifestyle factors and EC or CRC risk among individuals with lynch syndrome, who are at extraordinarily higher risk of developing EC or CRC. We conducted a systematic review of evidence related to weight status, weight change, dietary habits, and physic...
Published on Jun 1, 2019in Human Mutation4.45
Cristina Fortuno2
Estimated H-index: 2
Arcadi Cipponi3
Estimated H-index: 3
+ 9 AuthorsDavid M. Thomas49
Estimated H-index: 49
Published on Apr 8, 2019in Journal of Internal Medicine6.05
Gisela Barbany25
Estimated H-index: 25
(KI: Karolinska Institutet),
C. Arthur (KI: Karolinska Institutet)+ 5 AuthorsEmma Tham14
Estimated H-index: 14
(KI: Karolinska Institutet)
Published on Apr 1, 2019in Cancer Prevention Research3.87
Huei-Tzu Chien6
Estimated H-index: 6
(CGUST: Chang Gung University of Science and Technology),
Chi-Kuang Young1
Estimated H-index: 1
(Memorial Hospital of South Bend)
+ 4 AuthorsShiang-Fu Huang33
Estimated H-index: 33
(CGU: Chang Gung University)
Multiple primary tumors (MPTs), especially in the hypopharynx and esophagus, are challenging in head and neck cancer (HNC) patients. Alcohol and alcohol-metabolizing genes were reported to be related to upper digestive tract cancers. Here, we investigated whether the genotypes of alcohol-metabolizing enzymes (ADH1B, ADH1C and ALDH2) affected patients9 susceptibility to developing MPTs. We recruited 659 male HNC patients between March 1996 and February 2017. Age and gender-matched controls were a...
Published on Apr 1, 2019in British Journal of Cancer5.42
Jakob Nikolas Kather6
Estimated H-index: 6
(DKFZ: German Cancer Research Center),
Niels Halama18
Estimated H-index: 18
Significant progress in the development of new immunotherapies has led to successful clinical trials for malignant melanoma and non-small cell lung cancer; however, for the majority of solid tumours of the gastrointestinal tract, little or no progress has been seen. The efficacy of immunotherapies is limited by the complexities of a diverse set of immune cells, and interactions between the tumour cells and all other cells in the local microenvironment of solid tumours. A large fraction of immune...
Published on Apr 1, 2019in The Journal of Pathology5.94
Tsuyoshi Hamada27
Estimated H-index: 27
(UTokyo: University of Tokyo),
Jonathan A. Nowak21
Estimated H-index: 21
(Brigham and Women's Hospital)
+ 2 AuthorsShuji Ogino84
Estimated H-index: 84
Published on Mar 15, 2019in Journal of Medical Genetics5.90
Jiangrong Chen (SJTU: Shanghai Jiao Tong University), Chunchao Zhu (SJTU: Shanghai Jiao Tong University)+ 5 AuthorsZhifeng Shao40
Estimated H-index: 40
(SJTU: Shanghai Jiao Tong University)
Background Spasmolytic polypeptide-expressing metaplasia (SPEM) is present in more than 90% of resected gastric cancer tissues. However, although widely regarded as a pre-cancerous tissue, its genetic characteristics have not been well studied. Methods Immunohistochemistry using Trefoil factor 2 (TFF2) antibodies was used to identify TFF2-positive SPEM cells within SPEM glands in the stomach of Helicobacter felis (H. felis) -infected mice and human clinical samples. Laser microdissection was use...
Published on Mar 1, 2019in Nature Reviews Clinical Oncology34.11
Jake S. O’Donnell5
Estimated H-index: 5
(UQ: University of Queensland),
Michele W. L. Teng43
Estimated H-index: 43
(UQ: University of Queensland),
Mark J. Smyth127
Estimated H-index: 127
(UQ: University of Queensland)
Anticancer immunotherapies involving the use of immune-checkpoint inhibitors or adoptive cellular transfer have emerged as new therapeutic pillars within oncology. These treatments function by overcoming or relieving tumour-induced immunosuppression, thereby enabling immune-mediated tumour clearance. While often more effective and better tolerated than traditional and targeted therapies, many patients have innate or acquired resistance to immunotherapies. Cancer immunoediting is the process wher...
Published on Feb 1, 2019in Archives of Pharmacal Research2.46
Min-Kyue Shin (Yonsei University), Jae Ho Cheong35
Estimated H-index: 35
(University Health System)
Metabolic and genotoxic stresses that arise during tumor progression and anti-cancer treatment, respectively, can impose a selective pressure to promote cancer evolution in the tumor microenvironment. This process ultimately selects for the most “fit” clones, which generally have a cancer stem cell like phenotype with features of drug resistance, epithelial-mesenchymal transition, invasiveness, and high metastatic potential. From a bioenergetics perspective, these cancer stem-like cells (CSCs) e...
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