New Challenges and Inspired Answers for Anticancer Drug Discovery and Development
Open Access
- 5 September 2013
- journal article
- research article
- Published by Oxford University Press (OUP) in Japanese Journal of Clinical Oncology
- Vol. 43 (10), 945-953
- https://doi.org/10.1093/jjco/hyt131
Abstract
Many pharmaceutical companies worldwide specialize in oncology drug development and marketing. Among them, we have continued to take up the challenge of understanding the metabolism of pyrimidines as essential components of deoxyribonucleic acid for many years, and have provided unique products such as UFT® and TS-1 for cancer patients. Using our cumulative experience and knowledge, we are currently developing novel agents such as TAS-114, a dual inhibitor of deoxyuridine triphosphatase and dihydropyrimidine dehydrogenase, and TAS-102, a unique pyrimidine derivative inducing deoxyribonucleic acid dysfunction in cancer cells. Regarding molecular-targeted drugs, we have made huge efforts to establish ideal drug discovery platforms for the last several years. For kinase inhibitors, we established three core platforms such as a kinase-directed chemical library, a kinase assay panel and a target selection informatics system. The core platforms were further combined with peripheral technologies to measure essential parameters such as physicochemical properties, pharmacokinetics, efficacy and toxicities. Unique drug candidates have been identified at an early stage by assessing all important parameters. Several promising programs are proceeding simultaneously in the clinical or preclinical development stage such as TAS-115, a dual inhibitor of c-Met and vascular endothelial growth factor receptor, TAS-2104, a selective Aurora A inhibitor, TAS-117, an allosteric Akt inhibitor, TAS-2985, an irreversible fibroblast growth factor receptor inhibitor and TAS-2913, a T790M mutant selective epidermal growth factor receptor inhibitor. Other than kinase inhibitors, another drug discovery engine was established based on the fragment-based drug discovery technology. TAS-116, a new class of Hsp-90α/β inhibitor, is one of the products. Taiho's final goal is to provide innovative anticancer drugs together with companion diagnostics that are truly beneficial for patients.Keywords
This publication has 19 references indexed in Scilit:
- Identification of potential pharmacogenomic markers of clinical efficacy of 5‐fluorouracil in colorectal cancerInternational Journal of Cancer, 2011
- Irinotecan plus S-1 (IRIS) versus fluorouracil and folinic acid plus irinotecan (FOLFIRI) as second-line chemotherapy for metastatic colorectal cancer: a randomised phase 2/3 non-inferiority study (FIRIS study)The Lancet Oncology, 2010
- Hypoxia, DNA repair and genetic instabilityNature Reviews Cancer, 2008
- S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trialThe Lancet Oncology, 2008
- Adjuvant Chemotherapy for Gastric Cancer with S-1, an Oral FluoropyrimidineNew England Journal of Medicine, 2007
- Randomized controlled trial of adjuvant uracil–tegafur versus surgery alone for serosa-negative, locally advanced gastric cancerBritish Journal of Surgery, 2007
- Oral Uracil and Tegafur Plus Leucovorin Compared With Intravenous Fluorouracil and Leucovorin in Stage II and III Carcinoma of the Colon: Results From National Surgical Adjuvant Breast and Bowel Project Protocol C-06Journal of Clinical Oncology, 2006
- A Randomized Trial of Adjuvant Chemotherapy with Uracil–Tegafur for Adenocarcinoma of the LungNew England Journal of Medicine, 2004
- 5-Fluorouracil: mechanisms of action and clinical strategiesNature Reviews Cancer, 2003
- Thymidylate synthetase: Mechanism of inhibition by 5-fluoro-2′-deoxyuridylateBiochemical and Biophysical Research Communications, 1972