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

Josef Gillson; Yogambha Ramaswamy; Gurvinder Singh; Alemayehu A. Gorfe; Nick Pavlakis; Jaswinder Samra; Anubhav Mittal; Sumit Sahni

doi:10.3390/cancers12051341

Cancers (May 2020)

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

Josef Gillson,
Yogambha Ramaswamy,
Gurvinder Singh,
Alemayehu A. Gorfe,
Nick Pavlakis,
Jaswinder Samra,
Anubhav Mittal,
Sumit Sahni

Affiliations

Josef Gillson: Northern Clinical School, Faculty of Medicine and Health, University of Sydney, St Leonards 2065, NSW, Australia
Yogambha Ramaswamy: School of Biomedical Engineering, Faculty of Engineering, The University of Sydney 2006, Sydney, Australia
Gurvinder Singh: School of Biomedical Engineering, Faculty of Engineering, The University of Sydney 2006, Sydney, Australia
Alemayehu A. Gorfe: Department of Integrative Biology and Pharmacology, University of Texas Health Science Center Houston, Houston, TX 77030, USA
Nick Pavlakis: Northern Clinical School, Faculty of Medicine and Health, University of Sydney, St Leonards 2065, NSW, Australia
Jaswinder Samra: Northern Clinical School, Faculty of Medicine and Health, University of Sydney, St Leonards 2065, NSW, Australia
Anubhav Mittal: Northern Clinical School, Faculty of Medicine and Health, University of Sydney, St Leonards 2065, NSW, Australia
Sumit Sahni: Northern Clinical School, Faculty of Medicine and Health, University of Sydney, St Leonards 2065, NSW, Australia

DOI: https://doi.org/10.3390/cancers12051341
Journal volume & issue: Vol. 12, no. 5
p. 1341

Abstract

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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.

Published in Cancers

ISSN: 2072-6694 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.mdpi.com/journal/cancers/

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