Literature DB >> 28643779

Drugging the 'undruggable' cancer targets.

Chi V Dang1,2, E Premkumar Reddy3, Kevan M Shokat4, Laura Soucek5.   

Abstract

The term 'undruggable' was coined to describe proteins that could not be targeted pharmacologically. However, progress is being made to 'drug' many of these targets, and therefore more appropriate terms might be 'difficult to drug' or 'yet to be drugged'. Many desirable targets in cancer fall into this category, including the RAS and MYC oncogenes, and pharmacologically targeting these intractable proteins is now a key challenge in cancer research that requires innovation and the development of new technologies. In this Viewpoint article, we asked four scientists working in this field for their opinions on the most crucial advances, as well as the challenges and what the future holds for this important area of research.

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Year:  2017        PMID: 28643779      PMCID: PMC5945194          DOI: 10.1038/nrc.2017.36

Source DB:  PubMed          Journal:  Nat Rev Cancer        ISSN: 1474-175X            Impact factor:   60.716


  56 in total

1.  Cancer. Taking a back door to target Myc.

Authors:  Gerard Evan
Journal:  Science       Date:  2012-01-20       Impact factor: 47.728

Review 2.  Drugging the undruggable RAS: Mission possible?

Authors:  Adrienne D Cox; Stephen W Fesik; Alec C Kimmelman; Ji Luo; Channing J Der
Journal:  Nat Rev Drug Discov       Date:  2014-10-17       Impact factor: 84.694

Review 3.  Mechanisms of disease: Oncogene addiction--a rationale for molecular targeting in cancer therapy.

Authors:  I Bernard Weinstein; Andrew K Joe
Journal:  Nat Clin Pract Oncol       Date:  2006-08

Review 4.  Targeting the ubiquitin-proteasome system for cancer therapy.

Authors:  Min Shen; Sara Schmitt; Daniela Buac; Q Ping Dou
Journal:  Expert Opin Ther Targets       Date:  2013-07-04       Impact factor: 6.902

Review 5.  MYC on the path to cancer.

Authors:  Chi V Dang
Journal:  Cell       Date:  2012-03-30       Impact factor: 41.582

Review 6.  Expanding the number of 'druggable' targets: non-enzymes and protein-protein interactions.

Authors:  Leah N Makley; Jason E Gestwicki
Journal:  Chem Biol Drug Des       Date:  2013-01       Impact factor: 2.817

7.  Drugging MYCN through an allosteric transition in Aurora kinase A.

Authors:  William Clay Gustafson; Justin Gabriel Meyerowitz; Erin A Nekritz; Justin Chen; Cyril Benes; Elise Charron; Erin F Simonds; Robert Seeger; Katherine K Matthay; Nicholas T Hertz; Martin Eilers; Kevan M Shokat; William A Weiss
Journal:  Cancer Cell       Date:  2014-08-28       Impact factor: 31.743

8.  Multiple independent binding sites for small-molecule inhibitors on the oncoprotein c-Myc.

Authors:  Dalia I Hammoudeh; Ariele Viacava Follis; Edward V Prochownik; Steven J Metallo
Journal:  J Am Chem Soc       Date:  2009-06-03       Impact factor: 15.419

9.  Heterogeneity of resistance mutations detectable by nextgeneration sequencing in TKI-treated lung adenocarcinoma.

Authors:  Deborah A Belchis; Li-Hui Tseng; Thomas Gniadek; Lisa Haley; Parvez Lokhandwala; Peter Illei; Christopher D Gocke; Patrick Forde; Julie Brahmer; Frederic B Askin; James R Eshleman; Ming-Tseh Lin
Journal:  Oncotarget       Date:  2016-07-19

Review 10.  Strategies to Inhibit Myc and Their Clinical Applicability.

Authors:  Jonathan R Whitfield; Marie-Eve Beaulieu; Laura Soucek
Journal:  Front Cell Dev Biol       Date:  2017-02-23
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  205 in total

1.  Targeting and extending the eukaryotic druggable genome with natural products.

Authors:  Hendrik Luesch; John B MacMillan
Journal:  Nat Prod Rep       Date:  2020-06-24       Impact factor: 13.423

2.  Therapeutic potential of FLANC, a novel primate-specific long non-coding RNA in colorectal cancer.

Authors:  Martin Pichler; Cristian Rodriguez-Aguayo; Su Youn Nam; Mihnea Paul Dragomir; Recep Bayraktar; Simone Anfossi; Erik Knutsen; Cristina Ivan; Enrique Fuentes-Mattei; Sang Kil Lee; Hui Ling; Tina Catela Ivkovic; Guoliang Huang; Li Huang; Yoshinaga Okugawa; Hiroyuki Katayama; Ayumu Taguchi; Emine Bayraktar; Rajat Bhattacharya; Paola Amero; William Ruixian He; Anh M Tran; Petra Vychytilova-Faltejskova; Christiane Klec; Diana L Bonilla; Xinna Zhang; Sanja Kapitanovic; Bozo Loncar; Roberta Gafà; Zhihui Wang; Vittorio Cristini; Samir M Hanash; Menashe Bar-Eli; Giovanni Lanza; Ondrej Slaby; Ajay Goel; Isidore Rigoutsos; Gabriel Lopez-Berestein; George Adrian Calin
Journal:  Gut       Date:  2020-01-27       Impact factor: 23.059

3.  Identification of a small-molecule compound that inhibits homodimerization of oncogenic NAC1 protein and sensitizes cancer cells to anticancer agents.

Authors:  XiaoHui Wang; Cheng Ji; HongHan Zhang; Yu Shan; YiJie Ren; YanWei Hu; LiangRong Shi; LingChuan Guo; WeiDong Zhu; YuJuan Xia; BeiJia Liu; ZiYun Rong; BiLian Wu; ZhiJun Ming; XingCong Ren; JianXun Song; JinMing Yang; Yi Zhang
Journal:  J Biol Chem       Date:  2019-05-17       Impact factor: 5.157

Review 4.  Survivin at a glance.

Authors:  Sally P Wheatley; Dario C Altieri
Journal:  J Cell Sci       Date:  2019-04-04       Impact factor: 5.285

Review 5.  Inhibition of Nonfunctional Ras.

Authors:  Ruth Nussinov; Hyunbum Jang; Attila Gursoy; Ozlem Keskin; Vadim Gaponenko
Journal:  Cell Chem Biol       Date:  2021-01-12       Impact factor: 8.116

6.  MNT Optimization for Intracellular Delivery of Antibody Fragments.

Authors:  A V Ulasov; Y V Khramtsov; T N Lupanova; A D Tsvetkova; A A Rosenkranz; T A Slastnikova; G P Georgiev; A S Sobolev
Journal:  Dokl Biochem Biophys       Date:  2018-05-19       Impact factor: 0.788

7.  KRAS Suppression-Induced Degradation of MYC Is Antagonized by a MEK5-ERK5 Compensatory Mechanism.

Authors:  Angelina V Vaseva; Devon R Blake; Thomas S K Gilbert; Serina Ng; Galen Hostetter; Salma H Azam; Irem Ozkan-Dagliyan; Prson Gautam; Kirsten L Bryant; Kenneth H Pearce; Laura E Herring; Haiyong Han; Lee M Graves; Agnieszka K Witkiewicz; Erik S Knudsen; Chad V Pecot; Naim Rashid; Peter J Houghton; Krister Wennerberg; Adrienne D Cox; Channing J Der
Journal:  Cancer Cell       Date:  2018-11-12       Impact factor: 31.743

Review 8.  An overview of recent molecular dynamics applications as medicinal chemistry tools for the undruggable site challenge.

Authors:  Ugo Perricone; Maria Rita Gulotta; Jessica Lombino; Barbara Parrino; Stella Cascioferro; Patrizia Diana; Girolamo Cirrincione; Alessandro Padova
Journal:  Medchemcomm       Date:  2018-04-19       Impact factor: 3.597

9.  Targeting STAT3 anti-apoptosis pathways with organic and hybrid organic-inorganic inhibitors.

Authors:  Matthew B Minus; Haopei Wang; Jaime O Munoz; Alexandra M Stevens; Alicia E Mangubat-Medina; Michael J Krueger; Wei Liu; Moses M Kasembeli; Julian C Cooper; Mikhail I Kolosov; David J Tweardy; Michele S Redell; Zachary T Ball
Journal:  Org Biomol Chem       Date:  2020-05-06       Impact factor: 3.876

10.  Dual carrier-cargo hydrophobization and charge ratio optimization improve the systemic circulation and safety of zwitterionic nano-polyplexes.

Authors:  Meredith A Jackson; Sean K Bedingfield; Fang Yu; Mitchell E Stokan; Rachel E Miles; Elizabeth J Curvino; Ella N Hoogenboezem; Rachel H Bonami; Shrusti S Patel; Peggy L Kendall; Todd D Giorgio; Craig L Duvall
Journal:  Biomaterials       Date:  2018-11-10       Impact factor: 12.479

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