scholarly journals Tyrosine Kinase Inhibitors for EGFR Gene Mutation-Positive Non-SmallCell Lung Cancers: An Update for Recent Advances in Therapeutics

2015 ◽  
Vol 03 (01) ◽  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Gene Mutation ◽  
Kinase Inhibitors ◽  
Lung Cancers ◽  
Egfr Gene ◽  
Recent Advances ◽  
Egfr Gene Mutation

scholarly journals Efficiency integrated chemotherapy with EGFR receptor tyrosine kinase inhibitors in patients with non-small cell lung cancer and an activating EGFR gene mutation.

2021 ◽  
Vol 67 (2) ◽  
pp. 246-253
Author(s):  
Konstantin Laktionov ◽  
Denis Yudin ◽  
Yuliya Maevskaya ◽  
Lyubov` Vladimirova ◽  
Dimitr Marinov ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Gene Mutation ◽  
Kinase Inhibitors ◽  
Acquired Resistance ◽  
Egfr Mutations ◽  
Genetic Profile ◽  
Tumor Resistance ◽  
Egfr Gene ◽  
Egfr Gene Mutation

The EGFR gene mutation occurs in 15% of patients with NSCLC. Tumors with such a molecular genetic profile are characterized by high sensitivity to therapy with EGFR tyrosine kinase inhibitors. However, the majority of EGFRm+ patients develop resistance to 1-2 generation TKI therapy after 9-13 months. In our study, we considered an integrated regimen combined use chemotherapy and targeted therapy as a possible way to overcome acquired tumor resistance to TKIs of 1–2 generations. The study included patients with IIIB / IV stages of NSCLC with activating EGFR mutations.  Initially there were two months of treatment by gefitinib 250 mg daily. Then, after a 2-week drug-free period, 3 cycles of paclitaxel 175 mg / m2 and carboplatin AUC5 were administrated at days 71-113. Thereafter, gefitinib was re-started on day 135 and continued until disease progression. The median PFS was 20.- months (16.0-23.9 months, CI 95%).  One -year progression-free survival (PFS) in patients who completed the chemotherapy stage was 79,6 %, two-year PFS - 38,9%. Brain metastases among patients with a progression of the disease were observed in 12 people (28.6%). The data obtained confirm the promise of using integrated chemotherapy with TKIs as a way to overcome the development of acquired resistance to TKIs of 1–2 generations.

scholarly journals Drug Tolerance to EGFR Tyrosine Kinase Inhibitors in Lung Cancers with EGFR Mutations

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1590
Author(s):  
Kenichi Suda ◽  
Tetsuya Mitsudomi
Keyword(s):  
Lung Cancer ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Molecular Mechanisms ◽  
Kinase Inhibitors ◽  
Drug Tolerance ◽  
Lung Cancers ◽  
Egfr Tyrosine Kinase ◽  
Egfr Tyrosine Kinase Inhibitors ◽  
Egfr Mutated

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) serve as the standard of care for the first-line treatment of patients with lung cancers with EGFR-activating mutations. However, the acquisition of resistance to EGFR TKIs is almost inevitable, with extremely rare exceptions, and drug-tolerant cells (DTCs) that demonstrate reversible drug insensitivity and that survive the early phase of TKI exposure are hypothesized to be an important source of cancer cells that eventually acquire irreversible resistance. Numerous studies on the molecular mechanisms of drug tolerance of EGFR-mutated lung cancers employ lung cancer cell lines as models. Here, we reviewed these studies to generally describe the features, potential origins, and candidate molecular mechanisms of DTCs. The rapid development of an optimal treatment for EGFR-mutated lung cancer will require a better understanding of the underlying molecular mechanisms of the drug insensitivity of DTCs.

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