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      The Role of Feedback Loops in Targeted Therapy for Pancreatic Cancer

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          Abstract

          Pancreatic cancer is the leading cause of cancer-related deaths worldwide, with limited treatment options and low long-term survival rates. The complex and variable signal regulation networks are one of the important reasons why it is difficult for pancreatic cancer to develop precise targeted therapy drugs. Numerous studies have associated feedback loop regulation with the development and therapeutic response of cancers including pancreatic cancer. Therefore, we review researches on the role of feedback loops in the progression of pancreatic cancer, and summarize the connection between feedback loops and several signaling pathways in pancreatic cancer, as well as recent advances in the intervention of feedback loops in pancreatic cancer treatment, highlighting the potential of capitalizing on feedback loops modulation in targeted therapy for pancreatic cancer.

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          Most cited references98

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            Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data were collected by the National Center for Health Statistics. In 2017, 1,688,780 new cancer cases and 600,920 cancer deaths are projected to occur in the United States. For all sites combined, the cancer incidence rate is 20% higher in men than in women, while the cancer death rate is 40% higher. However, sex disparities vary by cancer type. For example, thyroid cancer incidence rates are 3-fold higher in women than in men (21 vs 7 per 100,000 population), despite equivalent death rates (0.5 per 100,000 population), largely reflecting sex differences in the "epidemic of diagnosis." Over the past decade of available data, the overall cancer incidence rate (2004-2013) was stable in women and declined by approximately 2% annually in men, while the cancer death rate (2005-2014) declined by about 1.5% annually in both men and women. From 1991 to 2014, the overall cancer death rate dropped 25%, translating to approximately 2,143,200 fewer cancer deaths than would have been expected if death rates had remained at their peak. Although the cancer death rate was 15% higher in blacks than in whites in 2014, increasing access to care as a result of the Patient Protection and Affordable Care Act may expedite the narrowing racial gap; from 2010 to 2015, the proportion of blacks who were uninsured halved, from 21% to 11%, as it did for Hispanics (31% to 16%). Gains in coverage for traditionally underserved Americans will facilitate the broader application of existing cancer control knowledge across every segment of the population. CA Cancer J Clin 2017;67:7-30. © 2017 American Cancer Society.
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              Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States.

              Cancer incidence and deaths in the United States were projected for the most common cancer types for the years 2020 and 2030 based on changing demographics and the average annual percentage changes in incidence and death rates. Breast, prostate, and lung cancers will remain the top cancer diagnoses throughout this time, but thyroid cancer will replace colorectal cancer as the fourth leading cancer diagnosis by 2030, and melanoma and uterine cancer will become the fifth and sixth most common cancers, respectively. Lung cancer is projected to remain the top cancer killer throughout this time period. However, pancreas and liver cancers are projected to surpass breast, prostate, and colorectal cancers to become the second and third leading causes of cancer-related death by 2030, respectively. Advances in screening, prevention, and treatment can change cancer incidence and/or death rates, but it will require a concerted effort by the research and healthcare communities now to effect a substantial change for the future. ©2014 American Association for Cancer Research.
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                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                16 May 2022
                2022
                : 12
                : 800140
                Affiliations
                [1] 1Department of Gastroenterology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine , Hangzhou, China
                [2] 2Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province , Hangzhou, China
                Author notes

                Edited by: Zheng Gong, Jackson Laboratory, United States

                Reviewed by: Fergal Kelleher, Trinity College Dublin, Ireland; Giulio Fracasso, University of Verona, Italy

                *Correspondence: Xiaofeng Zhang, zxf837@ 123456126.com ; Jianfeng Yang, yjf3303@ 123456zju.edu.cn

                This article was submitted to Gastrointestinal Cancers: Hepato Pancreatic Biliary Cancers, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2022.800140
                9148955
                35651786
                473f6bd0-e0a4-45bd-b452-da6e56561595
                Copyright © 2022 Gu, Shen, Xie, Zhang and Yang

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 25 November 2021
                : 11 April 2022
                Page count
                Figures: 7, Tables: 2, Equations: 0, References: 98, Pages: 13, Words: 6158
                Funding
                Funded by: Natural Science Foundation of Zhejiang Province , doi 10.13039/501100004731;
                Categories
                Oncology
                Review

                Oncology & Radiotherapy
                pancreatic cancer,feedback loops,targeted therapy,negative regulation,positive regulation

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