Signaling pathways and targeted therapies in lung squamous cell carcinoma: mechanisms and clinical trials DOI Creative Commons

Zhenyi Niu,

Runsen Jin,

Yan Zhang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Oct. 5, 2022

Lung cancer is the leading cause of cancer-related death across world. Unlike lung adenocarcinoma, patients with squamous cell carcinoma (LSCC) have not benefitted from targeted therapies. Although immunotherapy has significantly improved patients' outcomes, relatively low response rate and severe adverse events hinder clinical application this promising treatment in LSCC. Therefore, it vital importance to a better understanding mechanisms underlying pathogenesis LSCC as well inner connection among different signaling pathways, which will surely provide opportunities for more effective therapeutic interventions In review, new insights were given about classical pathways been proved other types but LSCC, including PI3K pathway, VEGF/VEGFR signaling, CDK4/6 pathway. Other may potentials also discussed, FGFR1 EGFR KEAP1/NRF2 Next, chromosome 3q, harbors two key differentiation markers SOX2 TP63 discussed its related potential targets. We provided some progress epigenetic therapies immune checkpoints blockade (ICB) Subsequently, we outlined combination strategies ICB Finally, prospects challenges exploration novel

Language: Английский

The 2021 WHO Classification of Lung Tumors: Impact of Advances Since 2015 DOI Creative Commons
Andrew G. Nicholson, Ming‐Sound Tsao, Mary Beth Beasley

et al.

Journal of Thoracic Oncology, Journal Year: 2021, Volume and Issue: 17(3), P. 362 - 387

Published: Nov. 20, 2021

Language: Английский

Citations

919
Treatment landscape of triple-negative breast cancer — expanded options, evolving needs DOI
Giampaolo Bianchini, Carmine De Angelis, Luca Licata

et al.

Nature Reviews Clinical Oncology, Journal Year: 2021, Volume and Issue: 19(2), P. 91 - 113

Published: Nov. 9, 2021

Language: Английский

Citations

809
Immune Checkpoint Inhibitors in Cancer Therapy DOI Creative Commons
Yavar Shiravand, Faezeh Khodadadi, Seyyed Mohammad Amin Kashani

et al.

Current Oncology, Journal Year: 2022, Volume and Issue: 29(5), P. 3044 - 3060

Published: April 24, 2022

The discovery of immune checkpoint proteins such as PD-1/PDL-1 and CTLA-4 represents a significant breakthrough in the field cancer immunotherapy. Therefore, humanized monoclonal antibodies, targeting these have been utilized successfully patients with metastatic melanoma, renal cell carcinoma, head neck cancers non-small lung cancer. US FDA has approved three different categories inhibitors (ICIs) PD-1 (Nivolumab, Pembrolizumab, Cemiplimab), PDL-1 (Atezolimumab, Durvalumab Avelumab), inhibitor (Ipilimumab). Unfortunately, not all respond favourably to drugs, highlighting role biomarkers Tumour mutation burden (TMB), expression, microbiome, hypoxia, interferon-γ, ECM predicting responses ICIs-based current study aims review literature updates on ICIs therapy.

Language: Английский

Citations

756
Clinical implications of T cell exhaustion for cancer immunotherapy DOI
Andrew Chow, Karlo Perica, Christopher A. Klebanoff

et al.

Nature Reviews Clinical Oncology, Journal Year: 2022, Volume and Issue: 19(12), P. 775 - 790

Published: Oct. 10, 2022

Language: Английский

Citations

516
NF-κB in biology and targeted therapy: new insights and translational implications DOI Creative Commons
Qing Guo, Yizi Jin, Xinyu Chen

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 4, 2024

Abstract NF-κB signaling has been discovered for nearly 40 years. Initially, was identified as a pivotal pathway in mediating inflammatory responses. However, with extensive and in-depth investigations, researchers have that its role can be expanded to variety of mechanisms, biological processes, human diseases, treatment options. In this review, we first scrutinize the research process signaling, summarize composition, activation, regulatory mechanism signaling. We investigate interaction other important pathways, including PI3K/AKT, MAPK, JAK-STAT, TGF-β, Wnt, Notch, Hedgehog, TLR The physiological pathological states well intricate involvement inflammation, immune regulation, tumor microenvironment, are also explicated. Additionally, illustrate how is involved cancers, autoimmune cardiovascular metabolic neurological COVID-19. Further, discuss therapeutic approaches targeting IKK inhibitors, monoclonal antibodies, proteasome nuclear translocation DNA binding TKIs, non-coding RNAs, immunotherapy, CAR-T. Finally, provide an outlook field hope present stereoscopic, comprehensive will inform future clinical practice.

Language: Английский

Citations

451
Therapeutic targets and biomarkers of tumor immunotherapy: response versus non-response DOI Creative Commons
Dongrui Wang,

Xianlin Wu,

Yingli Sun

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Sept. 19, 2022

Abstract Cancers are highly complex diseases that characterized by not only the overgrowth of malignant cells but also an altered immune response. The inhibition and reprogramming system play critical roles in tumor initiation progression. Immunotherapy aims to reactivate antitumor overcome escape mechanisms tumors. Represented checkpoint blockade adoptive cell transfer, immunotherapy has seen tremendous success clinic, with capability induce long-term regression some tumors refractory all other treatments. Among them, blocking therapy, represented PD-1/PD-L1 inhibitors (nivolumab) CTLA-4 (ipilimumab), shown encouraging therapeutic effects treatment various tumors, such as non-small lung cancer (NSCLC) melanoma. In addition, advent CAR-T, CAR-M novel methods, entered a new era. At present, evidence indicates combination multiple methods may be one way improve effect. However, overall clinical response rate still needs improvement, which warrants development designs well discovery biomarkers can guide prescription these agents. Learning from past failure both basic research is for rational design studies future. this article, we describe efforts manipulate against discuss different targets types exploited promote

Language: Английский

Citations

293
Multimodal integration of radiology, pathology and genomics for prediction of response to PD-(L)1 blockade in patients with non-small cell lung cancer DOI Creative Commons
R. Vanguri, Jia Luo, Andrew Aukerman

et al.

Nature Cancer, Journal Year: 2022, Volume and Issue: 3(10), P. 1151 - 1164

Published: Aug. 29, 2022

Immunotherapy is used to treat almost all patients with advanced non-small cell lung cancer (NSCLC); however, identifying robust predictive biomarkers remains challenging. Here we show the capacity of integrating medical imaging, histopathologic and genomic features predict immunotherapy response using a cohort 247 NSCLC multimodal baseline data obtained during diagnostic clinical workup, including computed tomography scan images, digitized programmed death ligand-1 immunohistochemistry slides known outcomes immunotherapy. Using domain expert annotations, developed computational workflow extract patient-level machine-learning approach integrate into risk prediction model. Our model (area under curve (AUC) = 0.80, 95% confidence interval (CI) 0.74-0.86) outperformed unimodal measures, tumor mutational burden (AUC 0.61, CI 0.52-0.70) score 0.73, 0.65-0.81). study therefore provides quantitative rationale for improve in expert-guided machine learning.

Language: Английский

Citations

197
Managing Resistance to Immune Checkpoint Inhibitors in Lung Cancer: Treatment and Novel Strategies DOI
Antonio Passaro, Julie R. Brahmer, Scott Antonia

et al.

Journal of Clinical Oncology, Journal Year: 2022, Volume and Issue: 40(6), P. 598 - 610

Published: Jan. 5, 2022

A proportion of patients with lung cancer experience long-term clinical benefit immune checkpoint inhibitors (ICIs). However, most develop disease progression during treatment or after discontinuation. Definitions resistance are heterogeneous according to different and biologic features. Primary acquired resistance, related tumor-intrinsic tumor-extrinsic mechanisms, identified previous response patterns timing occurrence. The determine differential approaches. To date, several combination therapies under development delay prevent the occurrence ICIs, including blockade coinhibitory signals, activation those costimulatory functions, modulation tumor microenvironment, targeting T-cell priming. Tailoring specific treatments distinctive mechanisms would be ideal improve design results trial. In this review, we reviewed available evidence on definitions, management ICIs in cancer. We also data novel strategies investigation setting.

Language: Английский

Citations

188
Tumor biomarkers for diagnosis, prognosis and targeted therapy DOI Creative Commons
Yue Zhou, Lei Tao, Jiahao Qiu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: May 20, 2024

Abstract Tumor biomarkers, the substances which are produced by tumors or body’s responses to during tumorigenesis and progression, have been demonstrated possess critical encouraging value in screening early diagnosis, prognosis prediction, recurrence detection, therapeutic efficacy monitoring of cancers. Over past decades, continuous progress has made exploring discovering novel, sensitive, specific, accurate tumor significantly promoted personalized medicine improved outcomes cancer patients, especially advances molecular biology technologies developed for detection biomarkers. Herein, we summarize discovery development including history conventional innovative used biomarker classification biomarkers based on tissue origins, application clinical management. In particular, highlight recent advancements biomarker-based anticancer-targeted therapies emerging as breakthroughs promising strategies. We also discuss limitations challenges that need be addressed provide insights perspectives turn into opportunities this field. Collectively, multiple emphasized review may guidance precision medicine, broaden horizons future research directions, expedite patients according their rather than organs origin.

Language: Английский

Citations

160
Cancer biomarkers: Emerging trends and clinical implications for personalized treatment DOI Open Access
Antonio Passaro, Maise Al Bakir, Emily G. Hamilton

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(7), P. 1617 - 1635

Published: March 1, 2024

Language: Английский

Citations

150