Emerging Approaches to Overcome Acquired Drug Resistance Obstacles to Osimertinib in Non-Small-Cell Lung Cancer

Author(s):  
Matin Shaikh ◽  
Yashodeep Shinde ◽  
Rahul Pawara ◽  
Malleshappa Noolvi ◽  
Sanjay Surana ◽  
...  
2020 ◽  
Author(s):  
Nicole M Hermance ◽  
Elizabeth A Crowley ◽  
Conor P Herlihy ◽  
Amity L Manning

AbstractChromosome instability, or CIN, defined as a high frequency of whole chromosome gains and losses, is prevalent in many solid tumors. CIN has been shown to promote intra-tumor heterogeneity and correspond with tumor aggressiveness, drug resistance and tumor relapse. However, whether CIN promotes the acquisition of genomic changes responsible for drug resistance remain unclear. Here we assess the role of CIN in the acquisition of drug resistance in non small cell lung cancer. We show that impairment of centromeric cohesion underlies the generation of whole chromosome segregation errors and CIN in non small cell lung cancer cells. Further, we demonstrate that centromere-specific enhancement of chromosome cohesion strongly suppresses CIN and reduces intra-tumor heterogeneity. We demonstrate that suppression of CIN has no impact on NSCLC cell proliferation in vitro nor in tumor initiation in mouse xenograft models. However, suppression of CIN alters the timing and molecular mechanism that drive acquired drug resistance. These findings suggest mechanisms to suppress CIN may serve as effective co-therapies to limit tumor evolution and sustain drug response.


2015 ◽  
Vol 75 (22) ◽  
pp. 4937-4948 ◽  
Author(s):  
Alexandra B. Lantermann ◽  
Dongshu Chen ◽  
Kaitlin McCutcheon ◽  
Greg Hoffman ◽  
Elizabeth Frias ◽  
...  

Author(s):  
Navika D. Shukla ◽  
Ameen A. Salahudeen ◽  
Sukhmani K. Padda ◽  
Joel W. Neal ◽  
Heather A. Wakelee ◽  
...  

2021 ◽  
Vol 567 ◽  
pp. 79-85
Author(s):  
Koujun Zhu ◽  
Jun Zhu ◽  
Jichun Geng ◽  
Yongjian Zhang ◽  
Yan Qin ◽  
...  

2018 ◽  
Vol 51 (6) ◽  
pp. 2509-2522 ◽  
Author(s):  
Shousen Hu ◽  
Yongliang Yuan ◽  
Zhizhen Song ◽  
Dan Yan ◽  
Xiangzhen Kong

Background/Aims: Drug resistance remains a main obstacle to the treatment of non- small cell lung cancer (NSCLC). The aim of this study was to identify the expression profiles of microRNAs (miRNAs) in drug-resistant NSCLC cell lines. Methods: The expression profiles of miRNAs in drug-resistant NSCLC cell lines were examined using miRNA sequencing, and the common dysregulated miRNAs in these cell lines were identified and analyzed by bioinformatics methods. Results: A total of 29 upregulated miRNAs and 36 downregulated miRNAs were found in the drug-resistant NSCLC cell lines, of which 26 upregulated and 36 downregulated miRNAs were found to be involved in the Ras signaling pathway. The expression levels, survival analysis, and receiver operating characteristic curve of the dysregulated miRNAs based on The Cancer Genome Atlas database for lung adenocarcinoma showed that hsa-mir-192, hsa-mir-1293, hsa-mir-194, hsa-mir-561, hsa-mir-205, hsa-mir-30a, and hsa-mir-30c were related to lung cancer, whereas only hsa-mir-1293 and hsa-mir-561 were not involved in drug resistance. Conclusion: The results of this study may provide novel biomarkers for drug resistance in NSCLC and potential therapies for overcoming drug resistance, and may also reveal the potential mechanisms underlying drug resistance in this disease.


Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 1160-1167
Author(s):  
Xing Chai ◽  
Xinru Zhang ◽  
Wenqian Li ◽  
Jin Chai

Abstract Lung cancer is the most common cause of cancer-related death. Non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) are the two major histological categories of lung cancers. Drug resistance is a great challenge for cancer treatment, and histological transformation from NSCLC to SCLC is one of the mechanisms underlying drug resistance in NSCLC patients. SCLC-transformed patients show combined characteristics of NSCLC and SCLC; however, they lack timely diagnoses and effective treatment strategies. Thus, we reviewed the clinical characteristics of SCLC transformation patients with a literature search to enhance clinical consciousness, diagnosis, and personalized treatment for patients with it.


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