Spotlight on Small-Cell Lung Cancer and Other Lung Neuroendocrine Neoplasms DOI Open Access
Lynnette Fernández-Cuesta, Alexandra Sexton‐Oates,

Leyla Bayat

et al.

American Society of Clinical Oncology Educational Book, Journal Year: 2023, Volume and Issue: 43

Published: May 1, 2023

Lung neuroendocrine neoplasms (NENs) encompass a spectrum of that are subdivided into the well-differentiated tumors comprising low- and intermediate-grade typical atypical carcinoids, respectively, poorly differentiated, high-grade carcinomas including large-cell small-cell lung carcinoma (SCLC). Here, we review current morphological molecular classifications NENs on basis updated WHO Classification Thoracic Tumors discuss emerging subclassifications profiling potential therapeutic implications. We focus efforts in subtyping SCLC, particularly aggressive tumor with few treatment options, recent advances therapy adoption immune checkpoint inhibitors frontline setting for patients extensive-stage SCLC. further highlight promising immunotherapy strategies SCLC currently under investigation.

Language: Английский

Clinical insights into small cell lung cancer: Tumor heterogeneity, diagnosis, therapy, and future directions DOI Open Access
Zsolt Megyesfalvi, Carl M. Gay, Helmut Popper

et al.

CA A Cancer Journal for Clinicians, Journal Year: 2023, Volume and Issue: 73(6), P. 620 - 652

Published: June 17, 2023

Abstract Small cell lung cancer (SCLC) is characterized by rapid growth and high metastatic capacity. It has strong epidemiologic biologic links to tobacco carcinogens. Although the majority of SCLCs exhibit neuroendocrine features, an important subset tumors lacks these properties. Genomic profiling SCLC reveals genetic instability, almost universal inactivation tumor suppressor genes TP53 RB1 , a mutation burden. Because early metastasis, only small fraction patients are amenable curative‐intent resection, individuals require adjuvant platinum‐etoposide chemotherapy. Therefore, vast currently being treated with chemoradiation or without immunotherapy. In disease confined chest, standard therapy includes thoracic radiotherapy concurrent Patients (extensive‐stage) combination chemotherapy plus immunotherapy anti‐programmed death‐ligand 1 monoclonal antibody. initially very responsive platinum‐based chemotherapy, responses transient because development drug resistance. recent years, authors have witnessed accelerating pace insights into disease, leading redefinition classification scheme. This emerging knowledge molecular subtypes potential define unique therapeutic vulnerabilities. Synthesizing new discoveries current biology clinical management may lead unprecedented advances in patient care. Here, present overview multimodal approaches SCLC, special focus on illuminating how advancements research could accelerate development.

Language: Английский

Citations

169
Emerging therapies targeting the delta-like ligand 3 (DLL3) in small cell lung cancer DOI Creative Commons
Charles M. Rudin, Martin Reck, Melissa L. Johnson

et al.

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: June 24, 2023

Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma with a poor prognosis. Initial responses to standard-of-care chemo-immunotherapy are, unfortunately, followed by rapid disease recurrence in most patients. Current treatment options are limited, no therapies specifically approved as third-line or beyond. Delta-like ligand 3 (DLL3), Notch inhibitory ligand, attractive therapeutic target because it overexpressed on the surface of SCLC cells minimal expression normal cells. Several DLL3-targeted being developed for and other carcinomas, including antibody-drug conjugates (ADCs), T-cell engager (TCE) molecules, chimeric antigen receptor (CAR) therapies. First, we discuss clinical experience rovalpituzumab tesirine (Rova-T), DLL3-targeting ADC, development which was halted due lack efficacy phase studies, view understanding lessons that can be garnered rapidly evolving landscape SCLC. We then review preclinical data several agents currently development, TCE molecules-tarlatamab (formerly known AMG 757), BI 764532, HPN328-and CAR therapy 119. conclude discussion future challenges opportunities therapies, utility DLL3 biomarker patient selection progression, potential rational combinatorial approaches enhance efficacy.

Language: Английский

Citations

80
Priming agents transiently reduce the clearance of cell-free DNA to improve liquid biopsies DOI
Carmen Martin-Alonso, Shervin Tabrizi,

Kan Xiong

et al.

Science, Journal Year: 2024, Volume and Issue: 383(6680)

Published: Jan. 18, 2024

Liquid biopsies enable early detection and monitoring of diseases such as cancer, but their sensitivity remains limited by the scarcity analytes cell-free DNA (cfDNA) in blood. Improvements to have primarily relied on enhancing sequencing technology ex vivo. We sought transiently augment level circulating tumor (ctDNA) a blood draw attenuating its clearance report two intravenous priming agents given 1 2 hours before recover more ctDNA. Our consist nanoparticles that act cells responsible for cfDNA DNA-binding antibodies protect cfDNA. In tumor-bearing mice, they greatly increase recovery ctDNA improve detecting small tumors.

Language: Английский

Citations

72
Methylation across the central dogma in health and diseases: new therapeutic strategies DOI Creative Commons
Ruochen Liu, Erhu Zhao,

Huijuan Yu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Aug. 24, 2023

The proper transfer of genetic information from DNA to RNA protein is essential for cell-fate control, development, and health. Methylation DNA, RNAs, histones, non-histone proteins a reversible post-synthesis modification that finetunes gene expression function in diverse physiological processes. Aberrant methylation caused by mutations or environmental stimuli promotes various diseases accelerates aging, necessitating the development therapies correct disease-driver imbalance. In this Review, we summarize operating system across central dogma, which includes writers, erasers, readers, reader-independent outputs. We then discuss how dysregulation contributes neurological disorders, cancer, aging. Current small-molecule compounds target modifiers show modest success certain cancers. methylome-wide action lack specificity lead undesirable biological effects cytotoxicity, limiting their therapeutic application, especially with monogenic cause different directions changes. Emerging tools capable site-specific manipulation hold great promise solve dilemma. With refinement delivery vehicles, these new are well positioned advance basic research clinical translation field.

Language: Английский

Citations

56
Accelerating the understanding of cancer biology through the lens of genomics DOI Creative Commons
Dongfang Wang, Baolin Liu, Zemin Zhang

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(8), P. 1755 - 1771

Published: April 1, 2023

Language: Английский

Citations

44
Tumor- and circulating-free DNA methylation identifies clinically relevant small cell lung cancer subtypes DOI Creative Commons
Simon Heeke, Carl M. Gay, Marcos R. Estecio

et al.

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(2), P. 225 - 237.e5

Published: Jan. 25, 2024

Small cell lung cancer (SCLC) is an aggressive malignancy composed of distinct transcriptional subtypes, but implementing subtyping in the clinic has remained challenging, particularly due to limited tissue availability. Given known epigenetic regulation critical SCLC programs, we hypothesized that subtype-specific patterns DNA methylation could be detected tumor or blood from patients. Using genomic-wide reduced-representation bisulfite sequencing (RRBS) two cohorts totaling 179 patients and using machine learning approaches, report a highly accurate methylation-based classifier (SCLC-DMC) can distinguish subtypes. We further adjust for circulating-free (cfDNA) subtype plasma. cfDNA (cfDMC), demonstrate phenotypes evolve during disease progression, highlighting need longitudinal tracking clinical treatment. These data establish used identify subtypes might guide precision therapy.

Language: Английский

Citations

42
Emerging advances in defining the molecular and therapeutic landscape of small-cell lung cancer DOI
Triparna Sen, Nobuyuki Takahashi,

Subhamoy Chakraborty

et al.

Nature Reviews Clinical Oncology, Journal Year: 2024, Volume and Issue: 21(8), P. 610 - 627

Published: July 4, 2024

Language: Английский

Citations

24
Impact of Higher Cell-Free DNA Yields on Liquid Biopsy Testing in Glioblastoma Patients DOI
J. Bryan Iorgulescu,

Timothy Blewett,

Kan Xiong

et al.

Clinical Chemistry, Journal Year: 2025, Volume and Issue: 71(1), P. 215 - 225

Published: Jan. 1, 2025

Minimally invasive molecular profiling using cell-free DNA (cfDNA) is increasingly important to the management of cancer patients; however, low sensitivity remains a major limitation, particularly for brain tumor patients. Transiently attenuating cfDNA clearance from body-thereby, allowing more be sampled-has been proposed improve performance liquid biopsy diagnostics. However, there paucity clinical data on effect higher recovery. Here, we investigated impact collecting greater quantities circulating (ctDNA) in "low-shedding" type glioblastoma by analyzing up approximately 15-fold plasma than routinely obtained clinically.

Language: Английский

Citations

3
Circulating Tumor DNA—A Novel Biomarker of Tumor Progression and Its Favorable Detection Techniques DOI Open Access
Xiaosha Wen, Huijie Pu, Quan Liu

et al.

Cancers, Journal Year: 2022, Volume and Issue: 14(24), P. 6025 - 6025

Published: Dec. 7, 2022

Cancer is the second leading cause of death in world and seriously affects quality life patients. The diagnostic techniques for tumors mainly include tumor biomarker detection, instrumental examination, tissue biopsy. In recent years, liquid technology represented by circulating DNA (ctDNA) has gradually replaced traditional with its advantages being non-invasive accurate, high specificity, sensitivity. ctDNA may carry throughout circulatory system through cell necrosis, apoptosis, exosome secretion, etc., carrying characteristic changes tumors, such as mutation, methylation, microsatellite instability, gene rearrangement, etc. this paper, mutation objects to describe preparation process before analysis, detection methods two gene-level changes, including a series enrichment derived from PCR, sequencing-based techniques, comprehensive are combined new materials. addition, role various stages cancer development summarized, early screening, diagnosis, molecular typing, prognosis prediction, recurrence monitoring, drug guidance. summary, an ideal involved whole development.

Language: Английский

Citations

39
The screening, identification, design and clinical application of tumor-specific neoantigens for TCR-T cells DOI Creative Commons
Jianping Li, Zhiwen Xiao,

Donghui Wang

et al.

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Aug. 30, 2023

Recent advances in neoantigen research have accelerated the development of tumor immunotherapies, including adoptive cell therapies (ACTs), cancer vaccines and antibody-based therapies, particularly for solid tumors. With next-generation sequencing bioinformatics technology, rapid identification prediction tumor-specific antigens (TSAs) has become possible. Compared with tumor-associated (TAAs), highly immunogenic TSAs provide new targets personalized immunotherapy can be used as prospective indicators predicting patient survival, prognosis, immune checkpoint blockade response. Here, characterization neoantigens clinical application neoantigen-based TCR-T strategies are summarized, current status, inherent challenges, translational potential these discussed.

Language: Английский

Citations

29