Pancreatic Cancer Research beyond DNA Mutations

Hiromichi Sato; Kazuki Sasaki; Tomoaki Hara; Yoshiko Tsuji; Yasuko Arao; Chihiro Otsuka; Yumiko Hamano; Mirei Ogita; Shogo Kobayashi; Eric di Luccio; Takaaki Hirotsu; Yuichiro Doki; Hidetoshi Eguchi; Taroh Satoh; Shizuka Uchida; Hideshi Ishii

doi:10.3390/biom12101503

Pancreatic Cancer Research beyond DNA Mutations

Biomolecules. 2022 Oct 17;12(10):1503. doi: 10.3390/biom12101503.

Authors

Hiromichi Sato^{1

2}, Kazuki Sasaki^{1

2}, Tomoaki Hara¹, Yoshiko Tsuji¹, Yasuko Arao¹, Chihiro Otsuka¹, Yumiko Hamano¹, Mirei Ogita¹, Shogo Kobayashi², Eric di Luccio³, Takaaki Hirotsu³, Yuichiro Doki², Hidetoshi Eguchi², Taroh Satoh², Shizuka Uchida⁴, Hideshi Ishii¹

Affiliations

¹ Department of Medical Data Science, Center of Medical Innovation and Translational Research, Osaka University Graduate School of Medicine, Suita, Yamadaoka 2-2, Osaka 565-0871, Japan.
² Department of Gastrointestinal Surgery, Osaka University Graduate School of Medicine, Suita, Yamadaoka 2-2, Osaka 565-0871, Japan.
³ Hirotsu Bio Science Inc., Chiyoda-Ku, Tokyo 102-0094, Japan.
⁴ Center for RNA Medicine, Department of Clinical Medicine, Aalborg University, Frederikskaj 10B, 2. (Building C), 2450 Copenhagen SV, Denmark.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is caused by genetic mutations in four genes: KRAS proto-oncogene and GTPase (KRAS), tumor protein P53 (TP53), cyclin-dependent kinase inhibitor 2A (CDKN2A), and mothers against decapentaplegic homolog 4 (SMAD4), also called the big 4. The changes in tumors are very complex, making their characterization in the early stages challenging. Therefore, the development of innovative therapeutic approaches is desirable. The key to overcoming PDAC is diagnosing it in the early stages. Therefore, recent studies have investigated the multifaced characteristics of PDAC, which includes cancer cell metabolism, mesenchymal cells including cancer-associated fibroblasts and immune cells, and metagenomics, which extend to characterize various biomolecules including RNAs and volatile organic compounds. Various alterations in the KRAS-dependent as well as KRAS-independent pathways are involved in the refractoriness of PDAC. The optimal combination of these new technologies is expected to help treat intractable pancreatic cancer.

Keywords: RNA; cancer metabolism; mutations; pancreatic ductal adenocarcinoma; sequencing.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Pancreatic Ductal* / metabolism
Cyclin-Dependent Kinases / metabolism
DNA / therapeutic use
Humans
Mutation
Pancreatic Neoplasms* / metabolism
Proto-Oncogene Proteins p21(ras) / genetics
Proto-Oncogene Proteins p21(ras) / metabolism
Tumor Suppressor Protein p53 / metabolism
Volatile Organic Compounds*

Substances

Tumor Suppressor Protein p53
Volatile Organic Compounds
Proto-Oncogene Proteins p21(ras)
DNA
Cyclin-Dependent Kinases

Grants and funding

This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (19K22658; 20H00541; 22H03146; 22K19559) and the Japan Agency for Medical Research and Development (AMED) (17cm0106414h0002; JP19lm0203007; JP20lm0203007; JP21lm0203007). Partial support was received from Princess Takamatsu Cancer Research Fund and Mitsubishi Foundation to H.I.