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Cancers
Volume 12
Issue 5
10.3390/cancers12051341
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Open AccessPerspective

Small Molecule KRAS Inhibitors: The Future for Targeted Pancreatic Cancer Therapy?

by
Josef Gillson
1,2,3,
Yogambha Ramaswamy
4,
Gurvinder Singh
4,
Alemayehu A. Gorfe
5,
Nick Pavlakis
1,2,6,7,
Jaswinder Samra
1,3,8,
Anubhav Mittal
1,3,8 and
Sumit Sahni
1,2,3,*
1
Northern Clinical School, Faculty of Medicine and Health, University of Sydney, St Leonards 2065, NSW, Australia
2
Bill Walsh Translational Cancer Research Laboratory, Kolling Institute of Medical Research, University of Sydney, St Leonards 2065, NSW, Australia
3
Australian Pancreatic Centre, St Leonards 2065, NSW, Australia
4
School of Biomedical Engineering, Faculty of Engineering, The University of Sydney 2006, Sydney, Australia
5
Department of Integrative Biology and Pharmacology, University of Texas Health Science Center Houston, Houston, TX 77030, USA
6
Northern Sydney Cancer Center, Royal North Shore Hospital, St Leonards 2065, NSW, Australia
7
Genesis Care, St Leonards and Frenchs Forest 2065, NSW, Australia
8
Upper GI Surgical Unit, Royal North Shore Hospital and North Shore Private Hospital, St Leonards 2065, NSW, Australia
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(5), 1341; https://doi.org/10.3390/cancers12051341
Received: 4 May 2020 / Revised: 21 May 2020 / Accepted: 21 May 2020 / Published: 24 May 2020
(This article belongs to the Special Issue Recent Advances in Pancreatic Ductal Adenocarcinoma)
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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest solid tumors in the world. Currently, there are no approved targeted therapies for PDAC. Mutations in Kirsten rat sarcoma viral oncogene homologue (KRAS) are known to be a major driver of PDAC progression, but it was considered an undruggable target until recently. Moreover, PDAC also suffers from drug delivery issues due to the highly fibrotic tumor microenvironment. In this perspective, we provide an overview of recent developments in targeting mutant KRAS and strategies to overcome drug delivery issues (e.g., nanoparticle delivery). Overall, we propose that the antitumor effects from novel KRAS inhibitors along with strategies to overcome drug delivery issues could be a new therapeutic way forward in PDAC. View Full-Text
Keywords: pancreatic ductal adenocarcinoma; KRAS inhibitors; targeted therapies; drug delivery; nanoparticles; anti-fibrotic therapies pancreatic ductal adenocarcinoma; KRAS inhibitors; targeted therapies; drug delivery; nanoparticles; anti-fibrotic therapies
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
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MDPI and ACS Style

Gillson, J.; Ramaswamy, Y.; Singh, G.; Gorfe, A.A.; Pavlakis, N.; Samra, J.; Mittal, A.; Sahni, S. Small Molecule KRAS Inhibitors: The Future for Targeted Pancreatic Cancer Therapy? Cancers 2020, 12, 1341. https://doi.org/10.3390/cancers12051341

AMA Style

Gillson J, Ramaswamy Y, Singh G, Gorfe AA, Pavlakis N, Samra J, Mittal A, Sahni S. Small Molecule KRAS Inhibitors: The Future for Targeted Pancreatic Cancer Therapy? Cancers. 2020; 12(5):1341. https://doi.org/10.3390/cancers12051341

Chicago/Turabian Style

Gillson, Josef; Ramaswamy, Yogambha; Singh, Gurvinder; Gorfe, Alemayehu A.; Pavlakis, Nick; Samra, Jaswinder; Mittal, Anubhav; Sahni, Sumit. 2020. "Small Molecule KRAS Inhibitors: The Future for Targeted Pancreatic Cancer Therapy?" Cancers 12, no. 5: 1341. https://doi.org/10.3390/cancers12051341

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