|LETTER TO THE EDITOR
|Year : 2021 | Volume
| Issue : 4 | Page : 799-800
Comprehensive genomic profiling of lung cancer: A key to better clinical management
Parul Gupta1, Amanjit Bal2, Navneet Singh1
1 Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
2 Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
|Date of Submission||01-Nov-2021|
|Date of Decision||15-Nov-2021|
|Date of Acceptance||24-Nov-2021|
|Date of Web Publication||29-Dec-2021|
Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Gupta P, Bal A, Singh N. Comprehensive genomic profiling of lung cancer: A key to better clinical management. Cancer Res Stat Treat 2021;4:799-800
|How to cite this URL:|
Gupta P, Bal A, Singh N. Comprehensive genomic profiling of lung cancer: A key to better clinical management. Cancer Res Stat Treat [serial online] 2021 [cited 2022 May 16];4:799-800. Available from: https://www.crstonline.com/text.asp?2021/4/4/799/334197
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the first line of treatment in patients with non-squamous non--small-cell lung carcinoma harboring mutations in the kinase domain of the EGFR gene. Patients treated with TKIs exhibit heterogeneous responses to these drugs, and almost all the patients develop disease progression within few months to years after the start of therapy. The common mechanisms associated with acquired resistance include acquisition of the T790M mutation (49%) in exon 20 of EGFR, transformation to small cell carcinoma (14%), mutations in PIK3CA (5%), and MET amplifications., Recently, Kapoor et al. published a case study in which a patient with an EGFR exon 19 deletion, treated with gefitinib, progressed within 5 months of starting treatment. Next-generation sequencing of the rebiopsied tissue revealed mutations in three genes of clinical relevance, namely EGFR, PIK3CA, and TP53. Among these, targeted therapy is available against mutations in the EGFR and PIK3CA genes. Simultaneous alterations in EGFR and PIK3CA genes in patients with lung cancer confer resistance to EGFR-TKIs, resulting in poor prognosis. This resistance mechanism to EGFR-TKIs is underexplored. Phosphoinositide 3-kinases (PI3K) are a family of enzymes with two subunits: a regulatory subunit and a catalytic subunit. The PIK3CA, PIK3CB, and PIK3CD genes encode the catalytic subunit of PI3K. Out of these, the most frequently altered gene is PIK3CA. Alterations in PIK3CA have been observed in various cancers, including breast and lung cancers.PIK3CA mutations are more frequent in breast cancers (40%), where they are associated with a poor response to human epidermal growth factor receptor 2 (HER2)-directed neoadjuvant therapy in patients with HER2-positive breast cancers.,The mutation frequency of PIK3CA varies among different subtypes of lung cancer (squamous cell carcinoma–11%; adenocarcinoma-2%–7%) and its clinical significance in patients with non-small cell lung cancer (NSCLC) is controversial.A meta-analysis revealed that PIK3CA mutation in addition to conferring resistance to EGFR-TKIs may influence the occurrence of lymph node metastasis. Hence, PIK3CA may serve as a promising prognostic and predictive marker in patients with NSCLC, especially in those with associated driver mutations.PIK3CA mutation has been found to be the most frequent concomitant alteration with other driver alterations in NSCLC.At present, PIK3CA mutation screening is not a part of routine molecular profiling of patients with lung cancer. As reported by Kapoor et al. the PIK3CA mutation in their case was reported post progression on NGS analysis of the metastatic tumor tissue, and it is not clear whether the mutation was present at baseline. Therefore, mutational analysis of genes other than the driver oncogenes, which are of prognostic importance (such as PIK3CA) should be included in routine molecular screening of patients with lung cancer. As advised by Kapoor et al., comprehensive genomic profiling of tumors should be done at baseline to identify any concomitant mutations which may result in poor prognosis. This will help clinicians choose better therapeutic options for patients. The case presented by Kapoor et al. successfully highlighted the lacunae in our current knowledge with regard to the management options for patients with analogous mutational profiles.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Rajendra A, Noronha V, Joshi A, Patil VM, Menon N, Prabhash K. Epidermal growth factor receptor-mutated non-small-cell lung cancer: A primer on contemporary management. Cancer Res Stat Treat 2019;2:36-53. [Full text]
Westover D, Zugazagoitia J, Cho BC, Lovly CM, Paz-Ares L. Mechanisms of acquired resistance to first- and second-generation EGFR tyrosine kinase inhibitors. Ann Oncol 2018;29:i10-9.
Kapoor A, Noronha V, Chougule A, Patil VM, Menon N, Joshi A, et al.
Molecular tumor board: Case 1-interplay of EGFR, MET and PD-L1 in non-small cell lung carcinoma. Cancer Res Stat Treat 2019;2:228-31. [Full text]
Kapoor A, Noronha V, Shetty OA, Kashyap L, Kumar A, Chandrani P, et al
. Concurrent EGFR
mutations in non-small-cell lung cancer. Cancer Res Stat Treat 2021;4:541-6. [Full text]
Kumar S, Bal A, Das A, Loriya I, Khare S, Bhattacharya S, et al.
Spectrum of PIK3CA/AKT mutations across molecular subtypes of triple-negative breast cancer. Breast Cancer Res Treat 2021;187:625-33.
Wang Y, Wang Y, Li J, Li J, Che G. Clinical significance of PIK3CA gene in non-small-cell lung cancer: A systematic review and meta-analysis. Biomed Res Int 2020;2020:3608241.
Loibl S, von Minckwitz G, Schneeweiss A, Paepke S, Lehmann A, Rezai M, et al.
PIK3CA mutations are associated with lower rates of pathologic complete response to anti-human epidermal growth factor receptor 2 (her2) therapy in primary HER2-overexpressing breast cancer. J Clin Oncol 2014;32:3212-20.
Arora S, Gogia A. Recent updates in systemic therapy of breast cancer: A brief narrative review. Cancer Res Stat Treat 2021;4:99-109. [Full text]
Eng J, Woo KM, Sima CS, Plodkowski A, Hellmann MD, Chaft JE, et al.
Impact of concurrent PIK3CA mutations on response to EGFR tyrosine kinase inhibition in EGFR-mutant lung cancers and on prognosis in oncogene-driven lung adenocarcinomas. J Thorac Oncol 2015;10:1713-9.