The KIF5B-RET Fusion Gene Mutation as a Novel Mechanism of Acquired EGFR Tyrosine Kinase Inhibitor Resistance in Lung Adenocarcinoma

Zhu, You‐cai; Wang, Wenxian; Zhang, Qu-Xia; Xu, C.; Zhuang, W.; Du, Ke; Chen, Gang; Lv, Tangfeng; Song, Yong

doi:10.1016/j.cllc.2018.09.011

Cited by 18 publications

(19 citation statements)

References 22 publications

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“…Chimeric RNAs could arise in the later stage of cancers after drug treatments that induce cancer cells' resistance specific to this drug and can drive the adaptive evolution of drug resistance cancer cells (Figure 2b). For example, in non-small-cell lung carcinoma (NSCLC), EGFR tyrosine kinase inhibitors (EGFR-TKI) are used as treatment, but in some cases, EGFR-TKI resistance is detected within one year of drug administration [78]. A recent case study reported that a 72-year-old male lung adenocarcinoma patient with an EGFR deletion mutation initially responded to EGFR-TKI treatment but later developed acquired resistance against EGFR-TKI.…”

Section: Functional Impact Of Chimeric Rnas In Cancer Heterogeneity and Drug Resistancementioning

confidence: 99%

“…A recent case study reported that a 72-year-old male lung adenocarcinoma patient with an EGFR deletion mutation initially responded to EGFR-TKI treatment but later developed acquired resistance against EGFR-TKI. Subsequently, a new fusion KIF5B-RET was identified from the repeated liquid biopsy samples from the post-treatment, suggesting that the emergence of this KIF5B-RET chimeric RNAs could potentially be associated with the EGFR-TKI drug resistance [78]. Further, several chimeric RNAs such as LDLR-RPL31P11, VCL-ADK, TAF15-AP2B1, and MYH9-EIF3D were detected from the RNA-seq data of the docetaxelresistant prostate cancer cell lines, which are not found to be associated with primary resistance and thought to be a crucial driver for acquired resistance [79].…”

Section: Functional Impact Of Chimeric Rnas In Cancer Heterogeneity and Drug Resistancementioning

confidence: 99%

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Emerging Role of Chimeric RNAs in Cell Plasticity and Adaptive Evolution of Cancer Cells

Mukherjee

Heng

Frenkel‐Morgenstern

2021

Cancers

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Gene fusions can give rise to somatic alterations in cancers. Fusion genes have the potential to create chimeric RNAs, which can generate the phenotypic diversity of cancer cells, and could be associated with novel molecular functions related to cancer cell survival and proliferation. The expression of chimeric RNAs in cancer cells might impact diverse cancer-related functions, including loss of apoptosis and cancer cell plasticity, and promote oncogenesis. Due to their recurrence in cancers and functional association with oncogenic processes, chimeric RNAs are considered biomarkers for cancer diagnosis. Several recent studies demonstrated that chimeric RNAs could lead to the generation of new functionality for the resistance of cancer cells against drug therapy. Therefore, targeting chimeric RNAs in drug resistance cancer could be useful for developing precision medicine. So, understanding the functional impact of chimeric RNAs in cancer cells from an evolutionary perspective will be helpful to elucidate cancer evolution, which could provide a new insight to design more effective therapies for cancer patients in a personalized manner.

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Section: Functional Impact Of Chimeric Rnas In Cancer Heterogeneity and Drug Resistancementioning

confidence: 99%

Section: Functional Impact Of Chimeric Rnas In Cancer Heterogeneity and Drug Resistancementioning

confidence: 99%

Emerging Role of Chimeric RNAs in Cell Plasticity and Adaptive Evolution of Cancer Cells

Mukherjee

Heng

Frenkel‐Morgenstern

2021

Cancers

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“… 47 , 48 The combination of second-line osimertinib with a selective RET inhibitor, pralsetinib, led to a decrease in cell viability in vitro; it was well tolerated and led to an impressive response with 78% tumor shrinkage at 8 weeks in two patients with EGFR exon 19 deletions: one with CCDC6-RET fusion identified on MGH Solid Fusion Assay 18 months after progression on second-line osimertinib; and another with NCOA4-RET fusion identified on NGS 2 years after progression on the combination afatinib and cetuximab. 49 Other reports described the fusion KIF5B-RET found on tissue 50 or liquid 51 biopsy as a potential mechanism of acquired resistance in patients with NSCLC with EGFR exon 19 deletions who progressed on EGFR inhibition with erlotinib 52 or icotinib. 51 The patient who progressed after 11 months of treatment with icotinib, had an SD for 2 months with the addition of cabozantinib.…”

Section: Ret Emergence As a Mechanism Of Acquired Resistance To Egfr Inhibitionmentioning

confidence: 99%

RET Fusion: Joining the Ranks of Targetable Molecular Drivers in NSCLC

Osta

Ramalingam

2020

JTO Clinical and Research Reports

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The era of precision medicine has resulted in the identification of a number of genomic alterations that can be targeted with novel therapies. In lung adenocarcinomas, a histology structure that accounts for nearly 50% of all cases of lung cancer, and a number of genomic targets have been linked with effective targeted therapies. For patients with advanced-stage lung adenocarcinomas, molecular testing is now a standard part of diagnostic workup; for patients that have specific driver molecular events, targeted therapies have resulted in substantial improvement in efficacy without excessive toxicity. RET gene fusions are present in approximately 1% to 2% of NSCLC. It is emerging as a new targetable driver for this population. Despite sensitivity to platinum-based chemotherapy and conflicting small reports regarding the efficacy of immune checkpoint inhibitors, there have been limited treatment approaches for this subset of patients. Multiple nonselective RET tyrosine kinase inhibitors exhibited modest anti-RET activity with an increased off-target toxicity profile that often required dose interruption, reduction, or treatment cessation. Recently, novel selective RET inhibitors pralsetinib (BLU-667) and selpercatinib (LOXO-292) have exhibited promising clinical activity with low adverse effect profile in early clinical trials. These new agents are poised to represent a new hope for this special subgroup with unmet needs.

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“…Plenty of researches had proved that EGFR tyrosine kinase inhibitor resistance, apoptosis, and ErbB signaling pathway played key roles in various cancers. [ 32 – 38 ] Thus, we indicated that autophagy may likely be considered as a tumor suppressor in the process of laryngeal cancer tumorigenesis. It is acknowledged that autophagy always inhibited tumorigenesis by activation of gene mutations or inactivation of ARGs.…”

Section: Discussionmentioning

confidence: 91%

An autophagy-related model of 4 key genes for predicting prognosis of patients with laryngeal cancer

2020

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The KIF5B-RET Fusion Gene Mutation as a Novel Mechanism of Acquired EGFR Tyrosine Kinase Inhibitor Resistance in Lung Adenocarcinoma

Cited by 18 publications

References 22 publications

Emerging Role of Chimeric RNAs in Cell Plasticity and Adaptive Evolution of Cancer Cells

Emerging Role of Chimeric RNAs in Cell Plasticity and Adaptive Evolution of Cancer Cells

RET Fusion: Joining the Ranks of Targetable Molecular Drivers in NSCLC

An autophagy-related model of 4 key genes for predicting prognosis of patients with laryngeal cancer

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