Intratumoral heterogeneity may be responsible for chemotherapy resistance in patients with small cell lung cancer

(University of Texas M. D. Anderson Cancer Center) A study at The University of Texas MD Anderson Cancer Center found that chemotherapy results in increased heterogeneity within small cell lung cancer, leading to the evolution of multiple resistance mechanisms.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news

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Condition:   IIIA Stage Non-small Cell Lung Cancer Intervention:   Drug: Sintilimab Injection Sponsor:   First Hospital of Jilin University Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Small cell lung cancer (SCLC) is strongly associated with tobacco smoking and represents approximately 15 % of all lung cancer diagnosis [1]. Unfortunately, the majority of patients with SCLC present with incurable stage IV disease and screening methods have shown to be ineffective [2]. In Western countries standard first-line combination treatment consists of cis- or carboplatin and etoposide [3]. Recently, the addition of the anti-PD-L1 antibody atezolizumab or durvalumab to chemotherapy has demonstrated a moderate improvement of overall survival (OS) and progression-free survival (PFS) leading to a recent EMA approval o...
Source: Lung Cancer - Category: Cancer & Oncology Authors: Source Type: research
ConclusionsThe immunoproteasome may be an effective therapeutic target in a subset of CR lung cancers. Proteasomal proteolytic activity may be a predictive marker for the efficacy of immunoproteasome inhibitors in cisplatin-resistant SCLC and NSCLC.
Source: Cancer Chemotherapy and Pharmacology - Category: Cancer & Oncology Source Type: research
Conclusions: Practice size and proportion of patients treated varied between oncologists, but those differences did not translate into significantly different survival outcomes for patients. PMID: 32218658 [PubMed - as supplied by publisher]
Source: Current Oncology - Category: Cancer & Oncology Tags: Curr Oncol Source Type: research
Conclusions: In the Canadian setting, the acceptance of rebiopsy on progression was high. Multiple rebiopsies were clinically feasible and could increase the yield for T790M mutation. The incidence of complications was low despite the most common site for rebiopsy being lung. PMID: 32218657 [PubMed - as supplied by publisher]
Source: Current Oncology - Category: Cancer & Oncology Tags: Curr Oncol Source Type: research
Authors: Zhang P, Tao H, Yu L, Zhou L, Zhu C Abstract Injectable implants with the ability to form in situ are one of the most promising carriers for the delivery of chemotherapeutic drugs to tumor sites. We have reported a novel injectable in situ-forming implant system composed of n-butyl-2-cyanoacrylate (NBCA), ethyl oleate, along with the sol-gel phase transition. The chemotherapeutic drug-loaded injectable NBCA ethyl oleate implant (INEI) exhibited excellent therapeutic efficacy for local chemotherapy. Herein, we utilize this INEI to carry N, N'-(Sulfonyldi-4,1-phenylene)bis(2-chloroacetamide) (TE-C-5003), whi...
Source: Drug Delivery - Category: Drugs & Pharmacology Tags: Drug Deliv Source Type: research
Objectives: The authors sought to quantify the treatment patterns and outcomes for limited-stage (LS) and extensive-stage (ES) small cell lung cancer (SCLC) in a real-world setting. Methods: A review was conducted using the Glans-Look Research Database of patients with SCLC managed at a tertiary cancer center in Canada from 2010 to 2016. Adherence was defined as the commencement of planned SCLC treatment. Rate of compliance with the Alberta Health Services, American Society of Clinical Oncology, and National Comprehensive Cancer Network SCLC treatment guidelines was evaluated. Outcomes were analyzed using the Kaplan-M...
Source: American Journal of Clinical Oncology - Category: Cancer & Oncology Tags: Original Articles: Thoracic Source Type: research
Somatic alterations in the epidermal growth factor receptor gene (EGFR) result in aberrant activation of kinase signaling and occur in ∼15% of non-small cell lung cancers (NSCLC). Patients diagnosed with EGFR-mutant NSCLC have good initial clinical response to EGFR tyrosine kinase inhibitors (EGFR TKIs), yet tumor recurrence is common and quick to develop. Mechanisms of acquired resistance to EGFR TKIs have been studied extensively over the past decade. Great progress has been made in understanding two major routes of therapeutic failure: additional genomic alterations in the EGFR gene and activation of alternative kin...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
In this study we analyzed and validated the cytogenetic alterations that arise after treatment in four lung and ovarian paired cisplatin-sensitive/resistant cell lines by 1-million microarray-based comparative genomic hybridization (array-CGH) and qRT-PCR methodologies. RNA-sequencing, functional transfection assays, and gene-pathway activity analysis were used to identify genes with a potential role in the development of this malignancy. The results were further explored in 55 lung and ovarian primary tumors and control samples, and in two extensive in silico databases. Long-term cell exposure to platinum induces the freq...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Conclusions: As a minimally invasive test, liquid biopsy identifies a high proportion of people with the EGFR T790M resistance mutation. This identification could better guide treatment for people with advanced NSCLC. However, its relatively low negative predictive value means it is best used as a triage test (i.e., followed by tissue biopsy if the liquid biopsy does not identify a resistance mutation). Liquid biopsy as a triage test is likely more effective than tissue biopsy alone. However, owing to the high cost of treatment, liquid biopsy may not be cost-effective. We estimated that publicly funding liquid biopsy as a ...
Source: Ontario Health Technology Assessment Series - Category: General Medicine Tags: Ont Health Technol Assess Ser Source Type: research
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