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World J Gastroenterol. Jul 28, 2022; 28(28): 3637-3643
Published online Jul 28, 2022. doi: 10.3748/wjg.v28.i28.3637
Effective combinations of anti-cancer and targeted drugs for pancreatic cancer treatment
Arata Nishimoto
Arata Nishimoto, Division of Basic Pharmaceutical Science, Department of Pharmacy, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Sanyo-Onoda City 756-0884, Yamaguchi, Japan
Author contributions: Nishimoto A wrote the manuscript.
Conflict-of-interest statement: There is no conflict of interest related to this minireview manuscript.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Arata Nishimoto, PhD, Professor, Division of Basic Pharmaceutical Science, Department of Pharmacy, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, 1-1-1 Daigaku-dori , Sanyo-Onoda City 756-0884, Yamaguchi, Japan. anishimo@rs.socu.ac.jp
Received: April 1, 2022
Peer-review started: April 1, 2022
First decision: May 9, 2022
Revised: June 6, 2022
Accepted: June 30, 2022
Article in press: June 30, 2022
Published online: July 28, 2022
Processing time: 116 Days and 18.2 Hours
Abstract

Pancreatic cancer is highly aggressive and lethal. Due to the lack of effective methods for detecting the disease at an early stage, pancreatic cancer is frequently diagnosed late. Gemcitabine has been the standard chemotherapy drug for patients with pancreatic cancer for over 20 years, but its anti-tumor effect is limited. Therefore, FOLFIRINOX (leucovorin, fluorouracil, irinotecan, oxaliplatin) as well as combination therapies using gemcitabine and conventional agents, such as cisplatin and capecitabine, has also been administered; however, these have not resulted in complete remission. Therefore, there is a need to develop novel and effective therapies for pancreatic cancer. Recently, some studies have reported that combinations of gemcitabine and targeted drugs have had significant anti-tumor effects on pancreatic cancer cells. As gemcitabine induced DNA damage response, the proteins related to DNA damage response can be suitable additional targets for novel gemcitabine-based combination therapy. Furthermore, KRAS/ RAF/MEK/ERK signaling triggered by oncogenic mutated KRAS and autophagy are frequently activated in pancreatic cancer. Therefore, these characteristics of pancreatic cancer are potential targets for developing effective novel therapies.

In this minireview, combinations of gemcitabine and targeted drugs to these characteristics, combinations of targeted drugs, combinations of natural products and anti-cancer agents, including gemcitabine, and combinations among natural products are discussed.

Keywords: Pancreatic cancer; Gemcitabine; Targeted drug; Combination therapy

Core Tip: Gemcitabine has been the standard chemotherapy drug for patients with pancreatic cancer; however, its effectiveness is limited. Therefore, various combination therapies involving gemcitabine and targeted drugs are being explored. A review of combination therapies based mainly on clinical studies has been published recently; therefore, this minireview focuses on the findings of basic studies and discusses combinations of gemcitabine and targeted drugs, combinations of targeted drugs, combinations of natural products and anti-cancer agents, including gemcitabine, and combinations among natural products.