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Molecular Analysis for Therapeutic Targets of Pancreatic Cancer

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Molecular Diagnosis and Targeting for Thoracic and Gastrointestinal Malignancy

Part of the book series: Current Human Cell Research and Applications ((CHCRA))

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Abstract

Pancreatic cancer is one of the most lethal malignancies in humans and still remains a challenging problem in targeted therapy compared to other malignancies. Accumulation of multiple molecular abnormalities is required for generation and progression of cancers, and one of the malignant hallmarks is the dependency on the abnormalities in cancer and host cells. Disruption of such addiction should cause specifically the cancer cell death, indicating a feasible rationale for molecular targeted therapy. Recent whole genomic, epigenomic, and transcriptomic studies identified four molecular subtypes of pancreatic cancer in respect to the cell lineages and signatures: (1) aberrantly differentiated endocrine exocrine subtype with KRAS signal network, (2) squamous trans-differentiation subtype with TP53 and KDM6A mutations, (3) immunogenic subtype with T-/B-cell signatures, and (4) pancreatic progenitor subtype with stemness identity. Based on the subtype classification, this review summarizes the molecular pathogenesis and therapeutic targets of pancreatic cancer. The subtype-directed precision medicine might be a promising strategy to treat the pancreatic cancer in the perspective of oncogenic and epigenetic pathways as well as immune regulatory checkpoints and stem cell fates.

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Acknowledgment

I sincerely appreciate the opportunity to write the review article. I thank all of my colleagues and collaborators at Tokyo Medical and Dental University, Osaka University, Kyushu University, and Brown Medical School. This work was supported by Grant-in-Aid for Scientific Research (A); Scientific Research on Innovative Areas from Ministry of Education, Culture, Sports, Science & Technology of Japan; Research Grant from the Princess Takamatsu Cancer Research Fund; and P-DIRECT and P-CREATE from Japan Agency for Medical Research and Development (AMED).

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  1. Department of Molecular Oncology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan

    Shinji Tanaka

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Correspondence to Shinji Tanaka .

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  1. Department of Nanobio Drug Discovery, Kyoto University, Sakyo-ku, Kyoto, Japan

    Yutaka Shimada

  2. Department of Surgery, Jikei University School of Medicine, Minato-ku, Tokyo, Japan

    Katsuhiko Yanaga

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Tanaka, S. (2018). Molecular Analysis for Therapeutic Targets of Pancreatic Cancer. In: Shimada, Y., Yanaga, K. (eds) Molecular Diagnosis and Targeting for Thoracic and Gastrointestinal Malignancy. Current Human Cell Research and Applications. Springer, Singapore. https://doi.org/10.1007/978-981-10-6469-2_8

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