Novel Spatial Approaches to Dissect the Lung Cancer Immune Microenvironment DOI Open Access
Idania Lubo, Sharia Hernandez, Ignacio I. Wistuba

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(24), P. 4145 - 4145

Published: Dec. 12, 2024

Lung cancer is a deadly disease with the highest rates of mortality. Over recent decades, better understanding biological mechanisms implicated in its pathogenesis has led to development targeted therapies and immunotherapy, resulting improvements patient outcomes. To understand lung tumor biology advance towards precision oncology, comprehensive profile necessary. In years, novel situ spatial multiomics approaches have emerged offering more detailed view location microenvironment cells, identifying their unique composition functional status. this sense, platforms been developed evaluate heterogeneity, gene expression, metabolic reprogramming, signaling pathway activation, cell–cell interactions, immune cell programs. research, several studies used these technologies locate cells associated them histological features that are relevant adenocarcinoma. These advancements may unveil further molecular will lead discovery biomarkers for treatment prediction prognosis. review, we provide an overview widely emerging pathology-based profiling how they enhance our response.

Language: Английский

Synthesis, Structural Modification, and Antismall Cell Lung Cancer Activity of 3-Arylisoquinolines with Dual Inhibitory Activity on Topoisomerase I and II DOI

Xuemei Deng,

Yuying Wang, Xi Yang

et al.

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

To overcome the compensatory effect between Topo I and II, one of reasons accounting for resistance SCLC patients, we are pioneering use 3-arylisoquinolines to develop dual inhibitors I/II management SCLC. A total 46 new compounds were synthesized. Compounds 3g (IC50 = 1.30 μM NCI-H446 cells 1.42 NCI-H1048 cells) 3x 1.32 2.45 selected detailed pharmacological investigation, due their outstanding cytotoxicity II inhibitory activity. effectively prevent cell proliferation, invasion, migration in vitro, byinducing mitochondrial apoptosis inhibiting PI3K/Akt/mTOR pathway. Their vivo tumor inhibition rate is comparable etoposide with lower toxicity. These results indicated potential therapeutic values as treating

Language: Английский

Citations

0
Long-term Complete Response to Pembrolizumab in Tumor Mutation Burden-high Small Cell Lung Cancer: A Case Report DOI Creative Commons

Kiyohide Komuta,

Kei Kunimasa, Akito Miyazaki

et al.

Case Reports in Oncology, Journal Year: 2025, Volume and Issue: 18(1), P. 443 - 448

Published: March 6, 2025

Introduction: Extensive-stage small-cell lung cancer (ED-SCLC) has a poor prognosis. There are few case reports on the therapeutic effect of pembrolizumab in advanced SCLC with high tumor mutation burden (TMB-high). Case Presentation: A 65-year-old woman was diagnosed ED-SCLC. The initial treatment regimen included carboplatin, etoposide, and durvalumab. Following administration durvalumab, etoposide discontinued due to an anaphylactic reaction immediately after its initiation. patient unable continue same switched cisplatin irinotecan therapy. FoundationOne panel test submitted at time, TMB-high detected. After four courses therapy, introduced, complete response (CR) maintained for 18 months. Conclusion: We report rare long-term ED-SCLC TMB-high, highlighting potential targeted immunotherapy such cases.

Language: Английский

Citations

0
Top advances of the year: Small cell lung cancer DOI Open Access
Misty Dawn Shields, Anne C. Chiang, Lauren A. Byers

et al.

Cancer, Journal Year: 2025, Volume and Issue: 131(6)

Published: March 4, 2025

Lung cancer remains the leading cause of cancer-related mortality in both men and women. Small cell lung (SCLC) is notorious for its early metastatic spread, aggressive biology, high frequency disease relapse, resulting inferior outcomes. In last few years, immunotherapy extensive-stage SCLC has offered a glimmer hope by improving survival approximately 2 months. 2024, therapeutic breakthroughs led to meaningful impact patients, offering potential long-term survival. Here, authors report top advances from including practice-changing implementation consolidative durvalumab limited-stage SCLC, lessons learned timing with radiation using LU-005, how delta-like ligand 3 bispecific T-cell engager tarlatamab affects relapsed landscape, addition lurbinectedin atezolizumab promising role antibody-drug conjugates. forward-thinking approach, discuss feasibility biomarker selection Southwest Oncology Group SWOG S1929 study precision medicine may inform treatments through neuroendocrine subtyping S2409 (PRISM) trial. Finally, they conclude exciting advocacy newly formed group Cell SMASHERS, amplifying support SCLC. scientific revolution arrived, spearheading new era change this disease.

Language: Английский

Citations

0
Prolonged Low-Dose Administration of FDA-Approved Drugs for Non-Cancer Conditions: A Review of Potential Targets in Cancer Cells DOI Open Access
Olivia Chang,

Sophia S. Cheon,

Nina Semenova

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2720 - 2720

Published: March 18, 2025

Though not specifically designed for cancer therapy, several FDA-approved drugs such as metformin, aspirin, and simvastatin have an effect in lowering the incidence of cancer. However, there is a great discrepancy between vitro concentrations needed to eliminate cells plasma concentration normally tolerated within body. At present, no universal explanation this mechanisms been proposed including targeting stem (CSCs) or cellular senescence. CSCs are with ability self-renewal differentiation known be resistant chemotherapy. Senescence response damage stress, characterized by permanent cell-cycle arrest apoptotic resistance. Although, both situations, few examples where low were most effective, satisfactory data support that either senescence target these drugs. In review, we concisely summarize used non-cancer conditions well their potential action incidence. addition, propose prolonged low-dose administration (PLDA) specific can useful effectively preventing metastasis formation selected patients.

Language: Английский

Citations

0
Comparative profiling of surgically resected primary tumors and their lymph node metastases in small-cell lung cancer DOI

Kristóf Csende,

Bence Ferencz, Kristiina Boettiger

et al.

ESMO Open, Journal Year: 2025, Volume and Issue: 10(4), P. 104514 - 104514

Published: March 18, 2025

Language: Английский

Citations

0
Recent advances in immunotherapy for small cell lung cancer DOI
Ziyuan Ren,

Shijie Shang,

Dawei Chen

et al.

Current Opinion in Oncology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 4, 2024

This review aims to provide an overview of recent advances in immunotherapy for small cell lung cancer (SCLC), with a focus on the current status immune checkpoint inhibitors (ICIs), novel combination strategies, and key biomarkers.

Language: Английский

Citations

2
Molecular Interactions of the Plant Steroid Hormone Epibrassinolide on Human Drug-Sensitive and Drug-Resistant Small-Cell Lung Carcinoma Cells DOI Open Access

David Sadava,

Shiuan Chen

Cancers, Journal Year: 2024, Volume and Issue: 16(22), P. 3812 - 3812

Published: Nov. 13, 2024

Background: Small-cell lung cancer (SCLC) has a poor prognosis because it is often diagnosed after spread and develops multi-drug resistance. Epibrassinolide (EB) plant steroid hormone with widespread distribution physiological effects. In plants, EB-activated gene expression occurs via GSK-mediated signaling pathway, similar to Wnt-β-catenin in animal cells that elevated cells. Methods: This mechanistic parallel prompted investigations of the molecular interactions EB on drug-sensitive (H69) multi-drug-resistant (VPA) SCLC Cellular were performed. Results: Pharmacologic between Wnt inhibitors IGC-011 PRI-724 determined by combination index method showed antagonism, indicating acts same pathway as these inhibitors. Following incubation drug-resistant EB, there was reduction β-catenin (e.g., 3.8 0.7 pg/µg protein), accompanied promoter activity, measured firefly luciferase-coupled element transfection. concentration regulated active form GSK3β. signaling, GSK3β converted inactive pGSK3β, thereby increasing β-catenin. After (pGSK3β) relative increase (GSK3β). vitro enzyme assays did not inhibit purified GSK3β, but non-competitive inhibition when cell extracts used source enzyme. indirect indicates may act blocking phosphorylation The protein levels three tumor markers, namely, NSE, CAV1, MYCL1, led significant markers. Two major effects are promotion apoptosis reversal drug Transcriptional analyses exposure increases genes encoding apoptotic inducers BAX FAS) effectors CASP3) reductions survivin). PGP1 MRP1, two membrane efflux pumps expressed cells, affect levels. an alter activity. human liver microsomes, metabolized NADPH-dependent oxidation UDPG-dependent glucuronidation, evidenced elimination cytotoxicity against Conclusions: Taken together, data indicate plants consumed diet, pharmacologically alters expression, substrate for microsomal modifications.

Language: Английский

Citations

2
Novel Spatial Approaches to Dissect the Lung Cancer Immune Microenvironment DOI Open Access
Idania Lubo, Sharia Hernandez, Ignacio I. Wistuba

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(24), P. 4145 - 4145

Published: Dec. 12, 2024

Lung cancer is a deadly disease with the highest rates of mortality. Over recent decades, better understanding biological mechanisms implicated in its pathogenesis has led to development targeted therapies and immunotherapy, resulting improvements patient outcomes. To understand lung tumor biology advance towards precision oncology, comprehensive profile necessary. In years, novel situ spatial multiomics approaches have emerged offering more detailed view location microenvironment cells, identifying their unique composition functional status. this sense, platforms been developed evaluate heterogeneity, gene expression, metabolic reprogramming, signaling pathway activation, cell–cell interactions, immune cell programs. research, several studies used these technologies locate cells associated them histological features that are relevant adenocarcinoma. These advancements may unveil further molecular will lead discovery biomarkers for treatment prediction prognosis. review, we provide an overview widely emerging pathology-based profiling how they enhance our response.

Language: Английский

Citations

0