|LETTERS TO EDITOR
|Year : 2021 | Volume
| Issue : 1 | Page : 185-186
Study of intransigence of the epidermal growth factor receptor in non-small cell lung cancer
Teesta Katte1, Divijendra Natha Reddy Sirigiri1, Avinash A Rasalkar2
1 Department of Biotechnology, BMS College of Engineering, Bengaluru, Karnataka, India
2 In-DNA Life Science Private Limited, Bhubaneswar, Odisha; Prabhat -Advanced Life Tech Solutions & Consultants, 4th Cross, Pharmacy College Road, Sangolli Rayann Nagar, Dharwad, Karnataka, India
|Date of Submission||26-Jan-2021|
|Date of Decision||12-Feb-2021|
|Date of Acceptance||23-Feb-2021|
|Date of Web Publication||26-Mar-2021|
Divijendra Natha Reddy Sirigiri
Department of Biotechnology, BMS College of Engineering, Bull Temple Road, Bengaluru - 560 019, Karnataka
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Katte T, Sirigiri DN, Rasalkar AA. Study of intransigence of the epidermal growth factor receptor in non-small cell lung cancer. Cancer Res Stat Treat 2021;4:185-6
|How to cite this URL:|
Katte T, Sirigiri DN, Rasalkar AA. Study of intransigence of the epidermal growth factor receptor in non-small cell lung cancer. Cancer Res Stat Treat [serial online] 2021 [cited 2021 Apr 23];4:185-6. Available from: https://www.crstonline.com/text.asp?2021/4/1/185/312068
We read with interest the article by Bondili et al. titled, “Resistance mechanisms to epidermal growth factor receptor (EGFR) inhibitors in non-small cell lung cancer.” In this article, the authors have reported the case of a 76-year-old woman with lung cancer harboring a mutation in the EGFR gene and described the patient's response to EGFR inhibitors and the resistance to therapy that developed over a period of time. The pleural nodule biopsy revealed an EGFR exon 19 in-frame deletion. Although the patient initially responded well to gefitinib, a first-generation EGFR tyrosine kinase inhibitor (TKI), over a period of time, she developed resistance to gefitinib and to third-generation EGFR inhibitors.
The authors have enumerated the various molecular events/pathways responsible for the development of resistance to EGFR TKIs. One of the most common mechanisms for acquired resistance to the first-generation TKIs is the T790M mutation in exon 20 of the EGFR gene. This mutation is seen in about 50%–60% of the patients., The T790M mutation occurs in the kinase domain of EGFR and has been shown to alter its affinity for ATP. The other, less common mechanisms of acquired resistance to EGFR TKIs include MET amplification, ERBB2 amplification, and transformation to small cell lung cancer, which have been well described by the authors.
After the patient developed resistance to the first- and second-generation TKIs, she was treated with osimertinib, a third-generation TKI. However, in due course, the patient developed resistance to osimertinib as well, and disease progression was confirmed with an omental biopsy. The authors have also comprehensively described the various mechanisms of resistance to third-generation TKIs, along with their possible treatment options. In addition to the mutations in the EGFR gene, the patient also harbored a mutation in the CTNNB1 gene. Although the authors have suggested that targeting the beta-catenin pathway could prevent or overcome the resistance to EGFR TKIs, it is not clear if this strategy was implemented in the present case. It would be interesting to know the authors' experience with this strategy in patients with lung cancer.
As discussed by the authors, niclosamide is an antihelminthic drug which has been shown to enhance the effect of first- and second-generation TKIs in patients with non-small cell lung carcinomas., The next-generation sequencing technology can be used for clinical exome sequencing or targeted sequencing with miRNA quantitative polymerase chain reaction panels (such as Exicon) at diagnosis, remission, and relapse to decipher the molecular determinants of resistance as well as to capture the profile of cancer stem cells responsible for the relapse. Given the heterogeneity of tumors, this strategy could help the oncologists to develop a dynamic patient/therapy monitoring system in collaboration with molecular biologists, translational biologists, and bioinformaticians for each cancer ward. However, this will only be beneficial if the patients are periodically followed up (every 3 months and analysis during remission is also important). It is essential to emphasize the importance of regular follow-up, especially in India and other Asian countries as patients are prone to defaulting on their follow-up once the major symptoms have resolved.
Thus, identification of the pathways/molecular signatures associated with chemotherapy outcomes plays an important role in selecting an appropriate course of treatment for the patient and improving their disease-free survival.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
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. Resistance mechanisms to epidermal growth factor receptor inhibitors in non-small cell lung cancer. Cancer Res Stat Treat 2020;3:801-7. [Full text]
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