Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: June 10, 2021

Abstract To flourish, cancers greatly depend on their surrounding tumor microenvironment (TME), and cancer-associated fibroblasts (CAFs) in TME are critical for cancer occurrence progression because of versatile roles extracellular matrix remodeling, maintenance stemness, blood vessel formation, modulation metabolism, immune response, promotion cell proliferation, migration, invasion, therapeutic resistance. CAFs highly heterogeneous stromal cells crosstalk with is mediated by a complex intricate signaling network consisting transforming growth factor-beta, phosphoinositide 3-kinase/AKT/mammalian target rapamycin, mitogen-activated protein kinase, Wnt, Janus kinase/signal transducers activators transcription, epidermal factor receptor, Hippo, nuclear kappa-light-chain-enhancer activated B cells, etc., pathways. These signals exhibit own special characteristics during the have potential to be targeted anticancer therapy. Therefore, comprehensive understanding these cascades interactions between necessary fully realize pivotal cancers. Herein, this review, we will summarize enormous amounts findings mediating its related targets or trials. Further, hypothesize three targeting strategies, including, namely, epithelial–mesenchymal common targets, sequential perturbation, crosstalk-directed paving way CAF-directed host cell-directed antitumor

Language: Английский

---

Combination strategies to maximize the benefits of cancer immunotherapy

Journal of Hematology & Oncology, Journal Year: 2021, Volume and Issue: 14(1)

Published: Sept. 27, 2021

Abstract Immunotherapies such as immune checkpoint blockade (ICB) and adoptive cell therapy (ACT) have revolutionized cancer treatment, especially in patients whose disease was otherwise considered incurable. However, primary secondary resistance to single agent immunotherapy often results treatment failure, only a minority of experience long-term benefits. This review article will discuss the relationship between response mechanisms immunotherapy. It also provide comprehensive on latest clinical status combination therapies (e.g., with chemotherapy, radiation targeted therapy), approved by US Food Drug Administration. an overview targeting cytokines other soluble immunoregulatory factors, ACT, virotherapy, innate modifiers vaccines, well that exploit alternative targets therapeutic modalities. Finally, this include stimulating insights from 2020 China Immuno-Oncology Workshop co-organized Chinese American Hematologist Oncologist Network (CAHON), National Medical Product Administration (NMPA) Tsinghua University School Medicine.

Language: Английский

---

The cancer-immunity cycle: Indication, genotype, and immunotype

Immunity, Journal Year: 2023, Volume and Issue: 56(10), P. 2188 - 2205

Published: Oct. 1, 2023

The cancer-immunity cycle provides a framework to understand the series of events that generate anti-cancer immune responses. It emphasizes iterative nature response where killing tumor cells by T initiates subsequent rounds antigen presentation and cell stimulation, maintaining active immunity adapting it evolution. Any step can become rate-limiting, rendering system unable control growth. Here, we update based on remarkable progress past decade. Understanding mechanism checkpoint inhibition has evolved, as our view dendritic in sustaining anti-tumor immunity. We additionally account for role microenvironment facilitating, not just suppressing, response, discuss importance considering tumor's immunological phenotype, "immunotype". While these new insights add some complexity cycle, they also provide targets research therapeutic intervention.

Language: Английский

---

Microenvironment drives cell state, plasticity, and drug response in pancreatic cancer

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

---

Cancer-associated fibroblasts in the single-cell era

Nature Cancer, Journal Year: 2022, Volume and Issue: 3(7), P. 793 - 807

Published: July 26, 2022

Language: Английский

---