Clonal heterogeneity in human pancreatic ductal adenocarcinoma and its impact on tumor progression

Beatty, GL, Werba, G., Lyssiotis, CA and Simeone, DM The biological basis of therapeutic resistance in pancreatic cancer. Development of genes. 35940-962 (2021).

Article CAS PubMed PubMed Central Google Scholar

Oberstein, PE & Olive, KP Pancreatic cancer: why is it so difficult to treat? There. Av. Gastroenterol. 6321-337 (2013).

Article PubMed PubMed Central Google Scholar

Siegel, RL, Giaquinto, AN and Jemal, A. Cancer Statistics, 2024. CA Cancer J. Clin. 7412-49 (2024).

PubMed Google Scholar

Conroy, T. et al. FOLFIRINOX or gemcitabine as adjuvant treatment for pancreatic cancer. N.Engl. J.Med. 3792395-2406 (2018).

Article CAS PubMed Google Scholar

Lomberk, G., Dusetti, N., Iovanna, J. and Urrutia, R. Emerging epigenomic landscapes of pancreatic cancer in the era of precision medicine. Nat. Common. 103875 (2019).

Article PubMed PubMed Central Google Scholar

Makohon-Moore, A. & Iacobuzio-Donahue, CA Biology and genetics of pancreatic cancer in an evolutionary perspective. Nat. Reverend Cancer 16553-565 (2016).

Article CAS PubMed PubMed Central Google Scholar

Waddell, N. et al. Entire genomes are redefining the mutational landscape of pancreatic cancer. Nature 518495-501 (2015).

Article CAS PubMed PubMed Central Google Scholar

Witkiewicz, AK et al. Whole exome sequencing of pancreatic cancer defines genetic diversity and therapeutic targets. Nat. Common. 66744 (2015).

Article CAS PubMed PubMed Central Google Scholar

Waters, AM & Der, CJ KRAS: the essential driver and therapeutic target of pancreatic cancer. Cold spring harb. Perspective. Med. 8a031435 (2018).

Article PubMed PubMed Central Google Scholar

Moffitt, RA et al. Virtual microdissection identifies distinct tumor- and stroma-specific pancreatic ductal adenocarcinoma subtypes. Nat. Broom. 471168-1178 (2015).

Article CAS PubMed PubMed Central Google Scholar

Bailey, P. et al. Genomic analyzes identify molecular subtypes of pancreatic cancer. Nature 53147-52 (2016).

Article CAS PubMed Google Scholar

Collisson, EA et al. Subtypes of pancreatic ductal adenocarcinoma and their different responses to treatment. Nat. Med. 17500-503 (2011).

Article CAS PubMed PubMed Central Google Scholar

Puleo, F. et al. Stratification of pancreatic ductal adenocarcinomas based on tumor and microenvironment characteristics. Gastroenterology 1551999-2013 (2018).

Article PubMed Google Scholar

Martens, S. et al. Different shades of pancreatic ductal adenocarcinoma, different pathways to precision therapeutic applications. Anne. Oncol. 301428-1436 (2019).

Article CAS PubMed Google Scholar

O’Kane, GM et al. GATA6 expression distinguishes classical and basal-like subtypes in advanced pancreatic cancer. Clin. Cancer Res. 264901-4910 (2020).

Article PubMed Google Scholar

Werba, G. et al. Single-cell RNA sequencing reveals the effects of chemotherapy on human pancreatic adenocarcinoma and its tumor microenvironment. Nat. Common. 14797 (2023).

Article CAS PubMed PubMed Central Google Scholar

Peng, J. et al. Single-cell RNA-seq highlights intra-tumoral heterogeneity and malignant progression of pancreatic ductal adenocarcinoma. Cell Res. 29725-738 (2019).

Article CAS PubMed PubMed Central Google Scholar

Cui Zhou, D. et al. Spatially restricted drivers and transitional cell populations cooperate with the microenvironment in untreated and chemoresistant pancreatic cancer. Nat. Broom. 541390-1405 (2022).

Article CAS PubMed PubMed Central Google Scholar

Moncada, R. et al. Integration of microarray-based spatial transcriptomics and single-cell RNA sequencing reveals the tissue architecture of pancreatic ductal adenocarcinomas. Nat. Biotechnology. 38333-342 (2020).

Article CAS PubMed Google Scholar

Shiau, C. et al. Spatially resolved analysis of pancreatic cancer identifies therapy-associated remodeling of the tumor microenvironment. Nat. Broom. 562466-2478 (2024).

Article CAS PubMed PubMed Central Google Scholar

Hwang, WL et al. Mononuclear and spatial transcriptome profiling of pancreatic cancer identifies multicellular dynamics associated with neoadjuvant therapy. Nat. Broom. 541178-1191 (2022).

Article CAS PubMed PubMed Central Google Scholar

Barkley, D. et al. Cancer cell states replicate across tumor types and form specific interactions with the tumor microenvironment. Nat. Broom. 541192-1201 (2022).

Article CAS PubMed PubMed Central Google Scholar

Chan-Seng-Yue, M. et al. Transcriptional phenotypes of pancreatic cancer depend on genomic events during tumor evolution. Nat. Broom. 52231-240 (2020).

Article CAS PubMed Google Scholar

Khaliq, AM et al. Spatial transcriptomic analysis of primary and metastatic pancreatic cancers highlights the microenvironmental heterogeneity of tumors. Nat. Broom. 562455-2465 (2024).

Article CAS PubMed Google Scholar

Pei, G. et al. Spatial mapping of transcriptomic plasticity in metastatic pancreatic cancer. Nature 642212-221 (2025).

Article CAS PubMed PubMed Central Google Scholar

Without love, IM et al. Single-cell atlas of human pancreatic cancer reveals association of CXCL10⁺ fibroblasts and basal subtype tumor cells. Clin. Cancer Res. 31756-772 (2025).

Article CAS PubMed PubMed Central Google Scholar

Karaayvaz, M. et al. Unraveling subclonal heterogeneity and aggressive disease states in TNBC through single-cell RNA sequencing. Nat. Common. 93588 (2018).

Article PubMed PubMed Central Google Scholar

Wang, R. et al. Single-cell dissection of intratumoral heterogeneity and lineage diversity in metastatic gastric adenocarcinoma. Nat. Med. 27141-151 (2021).

Article PubMed PubMed Central Google Scholar

Tickle, T., Tirosh, I., Georgescu, C., Brown, M. and Haas, B. inferCNV from the Trinity CTAT project (Klarman Cellular Observatory, Broad Institute of MIT and Harvard, 2019).

Raphaël, BJ et al. Integrated genomic characterization of pancreatic ductal adenocarcinoma. Cancer cell 32185-203 (2017).

Google Scholar article

Efremova, M., Vento-Tormo, M., Teichmann, SA & Vento-Tormo, R. CellPhoneDB: inferring cell-cell communication from combined expression of multi-subunit ligand-receptor complexes. Nat. Protocol. 151484-1506 (2020).

Article CAS PubMed Google Scholar

Johnston, RJ et al. The TIGIT immunoreceptor regulates antitumor and antiviral CD8⁺ Effector function of T cells. Cancer cell 26923-937 (2014).

Article CAS PubMed Google Scholar

Zhang, Q. et al. Blocking the TIGIT checkpoint receptor prevents NK cell exhaustion and elicits potent anti-tumor immunity. Nat. Immunol. 19723-732 (2018).

Article CAS PubMed Google Scholar

Akiyama, T. et al. Stromal reprogramming by double PDGFRα/β blockade enhances the effectiveness of anti-PD-1 immunotherapy in fibrotic tumors. Cancer Res. 83753-770 (2023).

Article CAS PubMed Google Scholar

Zhai, X. et al. Gas6/AXL pathway: immunological landscape and therapeutic potential. In front. Oncol. 131121130 (2023).

Article CAS PubMed PubMed Central Google Scholar

Kennel, KB, Bozlar, M., De Valk, AF & Greten, FR Cancer-associated fibroblasts in inflammation and antitumor immunity. Clin. Cancer Res. 291009-1016 (2023).

Article CAS PubMed PubMed Central Google Scholar

Dudley, AC & Griffioen, AW Modes of angiogenesis: an updated perspective. Angiogenesis 26477-480 (2023).

Article PubMed PubMed Central Google Scholar

Wirth, M., Mahboobi, S., Krämer, OH and Schneider, G. Concepts for targeting MYC in pancreatic cancer. Mol. Cancer there. 151792-1798 (2016).

Article CAS PubMed Google Scholar

Williams, M., Lomberk, G. and Urrutia, R. EGFR (ErbB) signaling pathways in pancreatic cancer pathogenesis. In Pancreatic cancer (ed. Neoptolemos, J. et al.) 383-408 https://doi.org/10.1007/978-1-4939-7193-0_15 (Springer, 2018).

Moraes, LA et al. Annexin-A1 enhances breast cancer growth and migration by promoting alternative…