Targeting KRAS in Pancreatic Cancer

被引:11
作者
Cowzer, Darren [1 ]
Zameer, Mohammed [1 ]
Conroy, Michael [1 ]
Kolch, Walter [2 ,3 ]
Duffy, Austin G. [1 ]
机构
[1] Mater Misericordiae Univ Hosp, Dept Med Oncol, Dublin D07R2WY, Ireland
[2] Univ Coll Dublin, Sch Med, Syst Biol Ireland, Belfield D04E1W1, Dublin, Ireland
[3] Univ Coll Dublin, Conway Inst Biomol & Biomed Res, Belfield D04E1W1, Dublin, Ireland
来源
JOURNAL OF PERSONALIZED MEDICINE | 2022年 / 12卷 / 11期
基金
爱尔兰科学基金会;
关键词
KRAS; pancreas cancer; targeted therapy; CELL LUNG-CANCER; ONCOGENIC KRAS; SOLID TUMORS; AMG; 510; INHIBITOR; THERAPY; COMBINATION; ADENOCARCINOMA; IMMUNOTHERAPY; GEMCITABINE;
D O I
10.3390/jpm12111870
中图分类号
R19 [保健组织与事业(卫生事业管理)];
学科分类号
摘要
Pancreatic cancer is mainly driven by mutations in the KRAS oncogene. While this cancer has shown remarkable therapy resistance, new approaches to inhibit mutated KRAS, KRAS activators and effectors show promise in breaking this therapeutic deadlock. Here, we review these innovations in therapies that target RAS signaling in pancreatic cancer from a clinical point of view. A number of promising approaches are currently in clinical trials or in clinical development. We focus on small-molecule drugs but also discuss immunotherapies and tumor vaccines.
引用
收藏
页数:11
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共 73 条
  • [1] Advances in the Genetics and Biology of Pancreatic Cancer
    Aguirre, Andrew J.
    Collisson, Eric A.
    [J]. CANCER JOURNAL, 2017, 23 (06) : 315 - 320
  • [2] Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma
    Aguirre, Andrew J.
    Hruban, Ralph H.
    Raphael, Benjamin J.
    [J]. CANCER CELL, 2017, 32 (02) : 185 - +
  • [3] A nanoparticle vaccine that targets neoantigen peptides to lymphoid tissues elicits robust antitumor T cell responses
    Arbelaez, Carlos A.
    Estrada, Juan
    Gessner, Melissa A.
    Glaus, Charles
    Morales, Agnieszka B.
    Mohn, Deanna
    Phee, Hyewon
    Lipford, J. Russell
    Johnston, James A.
    [J]. NPJ VACCINES, 2020, 5 (01)
  • [4] Acquired Resistance to KRASG12C Inhibition in Cancer
    Awad, M. M.
    Liu, S.
    Rybkin, I. I.
    Arbour, K. C.
    Dilly, J.
    Zhu, V. W.
    Johnson, M. L.
    Heist, R. S.
    Patil, T.
    Riely, G. J.
    Jacobson, J. O.
    Yang, X.
    Persky, N. S.
    Root, D. E.
    Lowder, K. E.
    Feng, H.
    Zhang, S. S.
    Haigis, K. M.
    Hung, Y. P.
    Sholl, L. M.
    Wolpin, B. M.
    Wiese, J.
    Christiansen, J.
    Lee, J.
    Schrock, A. B.
    Lim, L. P.
    Garg, K.
    Li, M.
    Engstrom, L. D.
    Waters, L.
    Lawson, J. D.
    Olson, P.
    Lito, P.
    Ou, S. -H. I.
    Christensen, J. G.
    Janne, P. A.
    Aguirre, A. J.
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2021, 384 (25) : 2382 - 2393
  • [5] Safety and antitumor activity of chimeric antigen receptor modified T cells in patients with chemotherapy refractory metastatic pancreatic cancer.
    Beatty, Gregory Lawrence
    O'Hara, Mark H.
    Nelson, Anne M.
    McGarvey, Maureen
    Torigian, Drew A.
    Lacey, Simon F.
    Melenhorst, Jan J.
    Levine, Bruce
    Plesa, Gabriela
    June, Carl H.
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (15)
  • [6] KRYSTAL-1: Updated activity and safety of adagrasib (MRTX849) in patients (Pts) with unresectable or metastatic pancreatic cancer (PDAC) and other gastrointestinal (GI) tumors harboring a KRASG12C mutation
    Bekaii-Saab, Tanios S.
    Spira, Alexander I.
    Yaeger, Rona
    Buchschacher, Gary L.
    McRee, Autumn Jackson
    Sabari, Joshua K.
    Johnson, Melissa Lynne
    Barve, Minal A.
    Hafez, Navid
    Velastegui, Karen
    Christensen, James G.
    Kheoh, Thian
    Der-Torossian, Hirak
    Rybkin, Igor I.
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2022, 40 (04)
  • [7] Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes
    Biankin, Andrew V.
    Waddell, Nicola
    Kassahn, Karin S.
    Gingras, Marie-Claude
    Muthuswamy, Lakshmi B.
    Johns, Amber L.
    Miller, David K.
    Wilson, Peter J.
    Patch, Ann-Marie
    Wu, Jianmin
    Chang, David K.
    Cowley, Mark J.
    Gardiner, Brooke B.
    Song, Sarah
    Harliwong, Ivon
    Idrisoglu, Senel
    Nourse, Craig
    Nourbakhsh, Ehsan
    Manning, Suzanne
    Wani, Shivangi
    Gongora, Milena
    Pajic, Marina
    Scarlett, Christopher J.
    Gill, Anthony J.
    Pinho, Andreia V.
    Rooman, Ilse
    Anderson, Matthew
    Holmes, Oliver
    Leonard, Conrad
    Taylor, Darrin
    Wood, Scott
    Xu, Qinying
    Nones, Katia
    Fink, J. Lynn
    Christ, Angelika
    Bruxner, Tim
    Cloonan, Nicole
    Kolle, Gabriel
    Newell, Felicity
    Pinese, Mark
    Mead, R. Scott
    Humphris, Jeremy L.
    Kaplan, Warren
    Jones, Marc D.
    Colvin, Emily K.
    Nagrial, Adnan M.
    Humphrey, Emily S.
    Chou, Angela
    Chin, Venessa T.
    Chantrill, Lorraine A.
    [J]. NATURE, 2012, 491 (7424) : 399 - 405
  • [8] A phase II open-label randomized study to assess the efficacy and safety of selumetinib (AZD6244 [ARRY-142886]) versus capecitabine in patients with advanced or metastatic pancreatic cancer who have failed first-line gemcitabine therapy
    Bodoky, Gyoergy
    Timcheva, Constanta
    Spigel, David Robert
    La Stella, Phillip Joseph
    Ciuleanu, Tudor Eliade
    Pover, G.
    Tebbutt, N. C.
    [J]. INVESTIGATIONAL NEW DRUGS, 2012, 30 (03) : 1216 - 1223
  • [9] Stable suppression of tumorigenicity by virus-mediated RNA interference
    Brummelkamp, TR
    Bernards, R
    Agami, R
    [J]. CANCER CELL, 2002, 2 (03) : 243 - 247
  • [10] Novel regulation of Ras proteins by direct tyrosine phosphorylation and dephosphorylation
    Buday, Laszlo
    Vas, Virag
    [J]. CANCER AND METASTASIS REVIEWS, 2020, 39 (04) : 1067 - 1073