For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
22
views
150
references
 Top references
cited by
101
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      734
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Complex roles of cAMP–PKA–CREB signaling in cancer

      review-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Cyclic adenosine monophosphate (cAMP) is the first discovered second messenger, which plays pivotal roles in cell signaling, and regulates many physiological and pathological processes. cAMP can regulate the transcription of various target genes, mainly through protein kinase A (PKA) and its downstream effectors such as cAMP-responsive element binding protein (CREB). In addition, PKA can phosphorylate many kinases such as Raf, GSK3 and FAK. Aberrant cAMP–PKA signaling is involved in various types of human tumors. Especially, cAMP signaling may have both tumor-suppressive and tumor-promoting roles depending on the tumor types and context. cAMP–PKA signaling can regulate cancer cell growth, migration, invasion and metabolism. This review highlights the important roles of cAMP–PKA–CREB signaling in tumorigenesis. The potential strategies to target this pathway for cancer therapy are also discussed.

          Related collections

          Most cited references150

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          Targeting mTOR for cancer therapy

          Hui Hua, Qingbin Kong, Hongying Zhang … (2019)
          Mechanistic target of rapamycin (mTOR) is a protein kinase regulating cell growth, survival, metabolism, and immunity. mTOR is usually assembled into several complexes such as mTOR complex 1/2 (mTORC1/2). In cooperation with raptor, rictor, LST8, and mSin1, key components in mTORC1 or mTORC2, mTOR catalyzes the phosphorylation of multiple targets such as ribosomal protein S6 kinase β-1 (S6K1), eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), Akt, protein kinase C (PKC), and type-I insulin-like growth factor receptor (IGF-IR), thereby regulating protein synthesis, nutrients metabolism, growth factor signaling, cell growth, and migration. Activation of mTOR promotes tumor growth and metastasis. Many mTOR inhibitors have been developed to treat cancer. While some of the mTOR inhibitors have been approved to treat human cancer, more mTOR inhibitors are being evaluated in clinical trials. Here, we update recent advances in exploring mTOR signaling and the development of mTOR inhibitors for cancer therapy. In addition, we discuss the mechanisms underlying the resistance to mTOR inhibitors in cancer cells.
          Article 0 comments Cited 344 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Molecular targeted therapy: Treating cancer with specificity

            Yi Jer Tan, Chern Oon, Yeuan Lee (2018)
            Molecular targeted therapies are revolutionized therapeutics which interfere with specific molecules to block cancer growth, progression, and metastasis. Many molecular targeted therapies approved by the Food and Drug Administration (FDA), have demonstrated remarkable clinical success in the treatment of a myriad of cancer types including breast, leukemia, colorectal, lung, and ovarian cancers. This review provides an update on the different types of molecular targeted therapies used in the treatment of cancer, focusing on the fundamentals of molecular targeted therapy, its mode of action in cancer treatment, as well as its advantages and limitations.
            Article 0 comments Cited 312 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Emerging insights of tumor heterogeneity and drug resistance mechanisms in lung cancer targeted therapy

              Zuan-Fu Lim, Patrick C Ma (2019)
              The biggest hurdle to targeted cancer therapy is the inevitable emergence of drug resistance. Tumor cells employ different mechanisms to resist the targeting agent. Most commonly in EGFR-mutant non-small cell lung cancer, secondary resistance mutations on the target kinase domain emerge to diminish the binding affinity of first- and second-generation inhibitors. Other alternative resistance mechanisms include activating complementary bypass pathways and phenotypic transformation. Sequential monotherapies promise to temporarily address the problem of acquired drug resistance, but evidently are limited by the tumor cells’ ability to adapt and evolve new resistance mechanisms to persist in the drug environment. Recent studies have nominated a model of drug resistance and tumor progression under targeted therapy as a result of a small subpopulation of cells being able to endure the drug (minimal residual disease cells) and eventually develop further mutations that allow them to regrow and become the dominant population in the therapy-resistant tumor. This subpopulation of cells appears to have developed through a subclonal event, resulting in driver mutations different from the driver mutation that is tumor-initiating in the most common ancestor. As such, an understanding of intratumoral heterogeneity—the driving force behind minimal residual disease—is vital for the identification of resistance drivers that results from branching evolution. Currently available methods allow for a more comprehensive and holistic analysis of tumor heterogeneity in that issues associated with spatial and temporal heterogeneity can now be properly addressed. This review provides some background regarding intratumoral heterogeneity and how it leads to incomplete molecular response to targeted therapies, and proposes the use of single-cell methods, sequential liquid biopsy, and multiregion sequencing to discover the link between intratumoral heterogeneity and early adaptive drug resistance. In summary, minimal residual disease as a result of intratumoral heterogeneity is the earliest form of acquired drug resistance. Emerging technologies such as liquid biopsy and single-cell methods allow for studying targetable drivers of minimal residual disease and contribute to preemptive combinatorial targeting of both drivers of the tumor and its minimal residual disease cells.
              Article 0 comments Cited 202 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Hongying Zhang: 695828920@qq.com
                Qingbin Kong: kongqingbincdut@163.com
                Jiao Wang: wangjiaobox@qq.com
                Yangfu Jiang: jyangfu@scu.edu.cn
                Hui Hua: huahuihuaxi@163.com
                Journal
                Journal ID (nlm-ta): Exp Hematol Oncol
                Journal ID (iso-abbrev): Exp Hematol Oncol
                Title: Experimental Hematology & Oncology
                Publisher: BioMed Central (London )
                ISSN (Electronic): 2162-3619
                Publication date (Electronic): 24 November 2020
                Publication date PMC-release: 24 November 2020
                Publication date Collection: 2020
                Volume: 9
                Electronic Location Identifier: 32
                Affiliations
                [1 ]GRID grid.13291.38, ISNI 0000 0001 0807 1581, Laboratory of Oncogene, National Clinical Research Center for Geriatrics, West China Hospital, , Sichuan University, ; Chengdu, China
                [2 ]GRID grid.411304.3, ISNI 0000 0001 0376 205X, School of Basic Medicine, , Chengdu University of Traditional Chinese Medicine, ; Chengdu, China
                [3 ]GRID grid.13291.38, ISNI 0000 0001 0807 1581, Laboratory of Stem Cell Biology, West China Hospital, , Sichuan University, ; Chengdu, 610041 China
                Article
                Publisher ID: 191
                DOI: 10.1186/s40164-020-00191-1
                PMC ID: 7684908
                PubMed ID: 33292604
                SO-VID: 780c96e8-b5ef-48ce-9fad-241617dd3db0
                Copyright © © The Author(s) 2020
                License:

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                Date received : 11 November 2020
                Date accepted : 19 November 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81872388
                Award Recipient :
                Categories
                Subject: Review
                Custom metadata
                issue-copyright-statement © The Author(s) 2020

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: camp,pka,creb,cancer
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: camp, pka, creb, cancer

                Comments

                Comment on this article

                scite_

                Similar content734

                See all similar

                Cited by101

                See all cited by

                Most referenced authors1,774

                See all reference authors