Research Topic

Challenges and Opportunities of TKIs in the Treatment of NSCLC Patients With Uncommon Mutations

About this Research Topic

The emergence of targeted therapy is a breakthrough in the field of lung cancer treatment undoubtedly, which has significantly prolonged the survival of patients with driver gene mutations. With the rapid development of next-generation sequencing technology and liquid biopsy, in addition to the common EGFR 19 exon deletion and L858R mutation, other uncommon mutations have attracted much more attention, such as EGFR 20 exon insertion, ALK gene rearrangement, ROS-1 and RET gene fusion, MET amplification, NTRK gene fusion, BRAF, HER2 and KRAS mutations. Many corresponding TKIs have been developed, which have also made a significant breakthrough in the precision treatment of NSCLC. For example, TAK-788 has been approved by the FDA for advanced NSCLC with EGFR 20 exon insertion. Alectinib offers surprising survival benefits for patients with ALK mutations. A lot of other TKIs targeting uncommon mutations of NSCLC have entered clinical trials, such as DS-8201, MRTX849, and so on. However, there are still many challenges in clinical settings. The unique tumor microenvironment of lung cancer patients with these uncommon mutations remains to be explored. How to overcome drug resistance and minimize adverse reactions caused by these targeted therapeutic drugs is a thorny problem to be solved. In addition, the application and efficacy of immunotherapy in this population have not been determined. On the other hand, while facing these challenges, new opportunities will also be discovered, bringing new hope for the treatment of lung cancer patients with uncommon driver mutations.

For this Research Topic, we would like to invite review papers or original research articles, including preclinical and clinical studies, to discuss the challenges and opportunities of TKIs in the treatment of NSCLC patients with uncommon mutations.


Please note: manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) will not be accepted in any of the sections of Frontiers in Oncology.


Keywords: Targeted Therapy, Lung Cancer, NSCLC, Molecular Targets, Chemotherapy, TKIs


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

The emergence of targeted therapy is a breakthrough in the field of lung cancer treatment undoubtedly, which has significantly prolonged the survival of patients with driver gene mutations. With the rapid development of next-generation sequencing technology and liquid biopsy, in addition to the common EGFR 19 exon deletion and L858R mutation, other uncommon mutations have attracted much more attention, such as EGFR 20 exon insertion, ALK gene rearrangement, ROS-1 and RET gene fusion, MET amplification, NTRK gene fusion, BRAF, HER2 and KRAS mutations. Many corresponding TKIs have been developed, which have also made a significant breakthrough in the precision treatment of NSCLC. For example, TAK-788 has been approved by the FDA for advanced NSCLC with EGFR 20 exon insertion. Alectinib offers surprising survival benefits for patients with ALK mutations. A lot of other TKIs targeting uncommon mutations of NSCLC have entered clinical trials, such as DS-8201, MRTX849, and so on. However, there are still many challenges in clinical settings. The unique tumor microenvironment of lung cancer patients with these uncommon mutations remains to be explored. How to overcome drug resistance and minimize adverse reactions caused by these targeted therapeutic drugs is a thorny problem to be solved. In addition, the application and efficacy of immunotherapy in this population have not been determined. On the other hand, while facing these challenges, new opportunities will also be discovered, bringing new hope for the treatment of lung cancer patients with uncommon driver mutations.

For this Research Topic, we would like to invite review papers or original research articles, including preclinical and clinical studies, to discuss the challenges and opportunities of TKIs in the treatment of NSCLC patients with uncommon mutations.


Please note: manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) will not be accepted in any of the sections of Frontiers in Oncology.


Keywords: Targeted Therapy, Lung Cancer, NSCLC, Molecular Targets, Chemotherapy, TKIs


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

29 November 2021 Abstract
28 January 2022 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

29 November 2021 Abstract
28 January 2022 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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