Pancreatic Cancer: Advances and Challenges

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2023 Apr 14

PMID 37059070

Authors

Christopher J Halbrook

Costas A Lyssiotis

Marina Pasca di Magliano

Anirban Maitra

Affiliations

Soon will be listed here.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers. Significant efforts have largely defined major genetic factors driving PDAC pathogenesis and progression. Pancreatic tumors are characterized by a complex microenvironment that orchestrates metabolic alterations and supports a milieu of interactions among various cell types within this niche. In this review, we highlight the foundational studies that have driven our understanding of these processes. We further discuss the recent technological advances that continue to expand our understanding of PDAC complexity. We posit that the clinical translation of these research endeavors will enhance the currently dismal survival rate of this recalcitrant disease.

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References

Mendt M, Kamerkar S, Sugimoto H, McAndrews K, Wu C, Gagea M . Generation and testing of clinical-grade exosomes for pancreatic cancer. JCI Insight. 2018; 3(8). PMC: 5931131. DOI: 10.1172/jci.insight.99263. View

Grunwald B, Devisme A, Andrieux G, Vyas F, Aliar K, McCloskey C . Spatially confined sub-tumor microenvironments in pancreatic cancer. Cell. 2021; 184(22):5577-5592.e18. DOI: 10.1016/j.cell.2021.09.022. View

Viale A, Pettazzoni P, Lyssiotis C, Ying H, Sanchez N, Marchesini M . Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function. Nature. 2014; 514(7524):628-32. PMC: 4376130. DOI: 10.1038/nature13611. View

Bryant K, Stalnecker C, Zeitouni D, Klomp J, Peng S, Tikunov A . Combination of ERK and autophagy inhibition as a treatment approach for pancreatic cancer. Nat Med. 2019; 25(4):628-640. PMC: 6484853. DOI: 10.1038/s41591-019-0368-8. View

Singh A, Greninger P, Rhodes D, Koopman L, Violette S, Bardeesy N . A gene expression signature associated with "K-Ras addiction" reveals regulators of EMT and tumor cell survival. Cancer Cell. 2009; 15(6):489-500. PMC: 2743093. DOI: 10.1016/j.ccr.2009.03.022. View

Momtaz P, OConnor C, Chou J, Capanu M, Park W, Bandlamudi C . Pancreas cancer and BRCA: A critical subset of patients with improving therapeutic outcomes. Cancer. 2021; 127(23):4393-4402. PMC: 9301324. DOI: 10.1002/cncr.33812. View

Aykut B, Pushalkar S, Chen R, Li Q, Abengozar R, Kim J . The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL. Nature. 2019; 574(7777):264-267. PMC: 6858566. DOI: 10.1038/s41586-019-1608-2. View

Santana-Codina N, Del Rey M, Kapner K, Zhang H, Gikandi A, Malcolm C . NCOA4-Mediated Ferritinophagy Is a Pancreatic Cancer Dependency via Maintenance of Iron Bioavailability for Iron-Sulfur Cluster Proteins. Cancer Discov. 2022; 12(9):2180-2197. PMC: 9437572. DOI: 10.1158/2159-8290.CD-22-0043. View

Olivares O, Mayers J, Gouirand V, Torrence M, Gicquel T, Borge L . Collagen-derived proline promotes pancreatic ductal adenocarcinoma cell survival under nutrient limited conditions. Nat Commun. 2017; 8:16031. PMC: 5504351. DOI: 10.1038/ncomms16031. View

10.

Lee J, Bernard V, Semaan A, Monberg M, Huang J, Stephens B . Elucidation of Tumor-Stromal Heterogeneity and the Ligand-Receptor Interactome by Single-Cell Transcriptomics in Real-world Pancreatic Cancer Biopsies. Clin Cancer Res. 2021; 27(21):5912-5921. PMC: 8563410. DOI: 10.1158/1078-0432.CCR-20-3925. View

11.

He S, Bhatt R, Brown C, Brown E, Buhr D, Chantranuvatana K . High-plex imaging of RNA and proteins at subcellular resolution in fixed tissue by spatial molecular imaging. Nat Biotechnol. 2022; 40(12):1794-1806. DOI: 10.1038/s41587-022-01483-z. View

12.

Hosein A, Dougan S, Aguirre A, Maitra A . Translational advances in pancreatic ductal adenocarcinoma therapy. Nat Cancer. 2022; 3(3):272-286. DOI: 10.1038/s43018-022-00349-2. View

13.

OHara M, OReilly E, Varadhachary G, Wolff R, Wainberg Z, Ko A . CD40 agonistic monoclonal antibody APX005M (sotigalimab) and chemotherapy, with or without nivolumab, for the treatment of metastatic pancreatic adenocarcinoma: an open-label, multicentre, phase 1b study. Lancet Oncol. 2021; 22(1):118-131. DOI: 10.1016/S1470-2045(20)30532-5. View

14.

Banh R, Biancur D, Yamamoto K, Sohn A, Walters B, Kuljanin M . Neurons Release Serine to Support mRNA Translation in Pancreatic Cancer. Cell. 2020; 183(5):1202-1218.e25. PMC: 8100789. DOI: 10.1016/j.cell.2020.10.016. View

15.

Singhi A, Koay E, Chari S, Maitra A . Early Detection of Pancreatic Cancer: Opportunities and Challenges. Gastroenterology. 2019; 156(7):2024-2040. PMC: 6486851. DOI: 10.1053/j.gastro.2019.01.259. View

16.

Yan L, Tu B, Yao J, Gong J, Carugo A, Bristow C . Targeting Glucose Metabolism Sensitizes Pancreatic Cancer to MEK Inhibition. Cancer Res. 2021; 81(15):4054-4065. PMC: 8338909. DOI: 10.1158/0008-5472.CAN-20-3792. View

17.

Collisson E, Bailey P, Chang D, Biankin A . Molecular subtypes of pancreatic cancer. Nat Rev Gastroenterol Hepatol. 2019; 16(4):207-220. DOI: 10.1038/s41575-019-0109-y. View

18.

Iacobuzio-Donahue C, Fu B, Yachida S, Luo M, Abe H, Henderson C . DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer. J Clin Oncol. 2009; 27(11):1806-13. PMC: 2668706. DOI: 10.1200/JCO.2008.17.7188. View

19.

Jiang H, Torphy R, Steiger K, Hongo H, Ritchie A, Kriegsmann M . Pancreatic ductal adenocarcinoma progression is restrained by stromal matrix. J Clin Invest. 2020; 130(9):4704-4709. PMC: 7456216. DOI: 10.1172/JCI136760. View

20.

Pushalkar S, Hundeyin M, Daley D, Zambirinis C, Kurz E, Mishra A . The Pancreatic Cancer Microbiome Promotes Oncogenesis by Induction of Innate and Adaptive Immune Suppression. Cancer Discov. 2018; 8(4):403-416. PMC: 6225783. DOI: 10.1158/2159-8290.CD-17-1134. View