Reprogramming the tumor microenvironment by genome editing for precision cancer therapy DOI Creative Commons
Ke Liu,

Jiajia Cui,

Yan Zhan

et al.

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: April 11, 2022

The tumor microenvironment (TME) is essential for immune escape by cells. It plays roles in development and metastasis. clinical outcomes of tumors are often closely related to individual differences the patient TME. Therefore, reprogramming TME cells their intercellular communication an attractive promising strategy cancer therapy. consist nonimmune These need be manipulated precisely safely improve Furthermore, it encouraging that this field has rapidly developed recent years with advent gene editing technologies. In review, we briefly introduce technologies systematically summarize applications precision therapy, including communication. cell can regulate differentiation, proliferation, function. Moreover, optimize infiltration specific recognition Thus, will pave way further breakthroughs

Language: Английский

Pancreatic cancer: Advances and challenges DOI Creative Commons
Christopher J. Halbrook, Costas A. Lyssiotis, Marina Pasca di Magliano

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(8), P. 1729 - 1754

Published: April 1, 2023

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

Language: Английский

Citations

554
Microenvironment drives cell state, plasticity, and drug response in pancreatic cancer DOI Creative Commons
Srivatsan Raghavan, Peter Winter, Andrew W. Navia

et al.

Cell, Journal Year: 2021, Volume and Issue: 184(25), P. 6119 - 6137.e26

Published: Dec. 1, 2021

Prognostically relevant RNA expression states exist in pancreatic ductal adenocarcinoma (PDAC), but our understanding of their drivers, stability, and relationship to therapeutic response is limited.To examine these attributes systematically, we profiled metastatic biopsies matched organoid models at single-cell resolution.In vivo, identify a new intermediate PDAC transcriptional cell state uncover distinct site-and state-specific tumor microenvironments (TMEs).Benchmarking against this reference map, reveal strong culture-specific biases cancer representation driven by altered TME signals.We restore heterogeneity adding back vivo-relevant factors show plasticity culture models.Further, prove that non-genetic modulation can strongly influence drug responses, uncovering vulnerabilities.This work provides broadly applicable framework for aligning across vivo ex settings, identifying drivers manipulating target associated vulnerabilities.

Language: Английский

Citations

348
Single-nucleus and spatial transcriptome profiling of pancreatic cancer identifies multicellular dynamics associated with neoadjuvant treatment DOI
William L. Hwang, Karthik A. Jagadeesh, Jimmy A. Guo

et al.

Nature Genetics, Journal Year: 2022, Volume and Issue: 54(8), P. 1178 - 1191

Published: July 28, 2022

Language: Английский

Citations

226
Neoadjuvant therapy for pancreatic cancer DOI
Christoph Springfeld, Cristina R. Ferrone, Matthew H. G. Katz

et al.

Nature Reviews Clinical Oncology, Journal Year: 2023, Volume and Issue: 20(5), P. 318 - 337

Published: March 17, 2023

Language: Английский

Citations

211
Tumor Microenvironment in Pancreatic Cancer Pathogenesis and Therapeutic Resistance DOI Creative Commons
Mara H. Sherman, Gregory L. Beatty

Annual Review of Pathology Mechanisms of Disease, Journal Year: 2022, Volume and Issue: 18(1), P. 123 - 148

Published: Sept. 21, 2022

Pancreatic ductal adenocarcinoma (PDAC) features a prominent stromal microenvironment with remarkable cellular and spatial heterogeneity that meaningfully impacts disease biology treatment resistance. Recent advances in tissue imaging capabilities, single-cell analytics, modeling have shed light on organizing principles shape the complexity of PDAC tumors. These insights into functional dependencies coordinate cancer cell relationships exist between cells extracellular matrix components present tumors are expected to unveil therapeutic vulnerabilities. We review recent field discuss current understandings mechanisms by which tumor shapes pathogenesis therapy

Language: Английский

Citations

199
Therapeutic developments in pancreatic cancer DOI
Zilun Hu, Eileen M. O’Reilly

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2023, Volume and Issue: 21(1), P. 7 - 24

Published: Oct. 5, 2023

Language: Английский

Citations

128
Spatial biology of cancer evolution DOI
Zaira Seferbekova, Artem Lomakin, Lucy Yates

et al.

Nature Reviews Genetics, Journal Year: 2022, Volume and Issue: 24(5), P. 295 - 313

Published: Dec. 9, 2022

Language: Английский

Citations

118
Discovering dominant tumor immune archetypes in a pan-cancer census DOI Creative Commons
Alexis J. Combes, Bushra Samad, Jessica Tsui

et al.

Cell, Journal Year: 2021, Volume and Issue: 185(1), P. 184 - 203.e19

Published: Dec. 27, 2021

Language: Английский

Citations

115
Single-cell RNA sequencing reveals the effects of chemotherapy on human pancreatic adenocarcinoma and its tumor microenvironment DOI Creative Commons
Gregor Werba,

Daniel Weissinger,

Emily Kawaler

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Feb. 13, 2023

The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC) is a complex ecosystem that drives progression; however, in-depth single cell characterization of the PDAC TME and its role response to therapy lacking. Here, we perform single-cell RNA sequencing on freshly collected human samples either before or after chemotherapy. Overall, find heterogeneous mixture basal classical cancer subtypes, along with distinct cancer-associated fibroblast macrophage subpopulations. Strikingly, basal-like cells exhibit similar transcriptional responses chemotherapy do not demonstrate shift towards program among treated samples. We observe decreased ligand-receptor interactions samples, particularly between TIGIT CD8 + T receptor cells, identify as major inhibitory checkpoint molecule cells. Our results suggest profoundly impacts may promote resistance immunotherapy.

Language: Английский

Citations

104
An invasive zone in human liver cancer identified by Stereo-seq promotes hepatocyte–tumor cell crosstalk, local immunosuppression and tumor progression DOI Creative Commons
Liang Wu, Jiayan Yan, Yinqi Bai

et al.

Cell Research, Journal Year: 2023, Volume and Issue: 33(8), P. 585 - 603

Published: June 19, 2023

Abstract Dissecting and understanding the cancer ecosystem, especially that around tumor margins, which have strong implications for cell infiltration invasion, are essential exploring mechanisms of metastasis developing effective new treatments. Using a novel border scanning digitization model enabled by nanoscale resolution-SpaTial Enhanced REsolution Omics-sequencing (Stereo-seq), we identified 500 µm-wide zone centered in patients with liver cancer, referred to as “the invasive zone”. We detected immunosuppression, metabolic reprogramming, severely damaged hepatocytes this zone. also subpopulation increased expression serum amyloid A1 A2 (referred collectively SAAs) located close on paratumor side. Overexpression CXCL6 adjacent malignant cells could induce activation JAK-STAT3 pathway nearby hepatocytes, subsequently caused SAAs’ overexpression these hepatocytes. Furthermore, secretion SAAs lead recruitment macrophages M2 polarization, further promoting local potentially resulting progression. Clinical association analysis additional five independent cohorts primary secondary ( n = 423) showed had worse prognosis. Further vivo experiments using mouse models situ confirmed knockdown genes encoding decreased macrophage accumulation delayed growth. The identification characterization human not only add an important layer regarding invasion metastasis, but may pave way therapeutic strategies advanced other solid tumors.

Language: Английский

Citations

103