|LETTER TO EDITOR
|Year : 2021 | Volume
| Issue : 1 | Page : 177-179
RET gene fusions/rearrangements as biomarkers for lung carcinoma
Avinash A Rasalkar1, Saloni Bhatia2, Divijendra Natha Reddy Sirigiri2
1 In- DNA Life Science Private Limited; Prabhat -Advanced Life Tech Solutions & Consultants, 4th Cross, Pharmacy College Road, Sangolli Rayann Nagar, Dharwad, Karnataka, India
2 Department of Biotechnology, BMS college of Engineering, Bull temple road, Bengaluru, Karnataka, India
|Date of Submission||23-Jan-2021|
|Date of Decision||11-Feb-2021|
|Date of Acceptance||11-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
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Rasalkar AA, Bhatia S, Reddy Sirigiri DN. RET gene fusions/rearrangements as biomarkers for lung carcinoma. Cancer Res Stat Treat 2021;4:177-9
Batra et al., in their case series, have reported the utility of RET fusions/rearrangements as a potential biomarker for lung carcinomas. In this study, the next-generation sequencing (NGS) technology was used to precisely identify the RET fusions in the tumors of patients with lung cancer. From the perspective of personalized or precision medicine for cancer management, RET fusions can have lifesaving significance as a biomarker. However, a comprehensive study with a larger sample size and rigorous statistical analysis is required to establish RET fusions as a reliable biomarker in patients with lung cancers. Despite its precision, at present, NGS may not be a viable option for routine diagnosis. Therefore, a polymerase chain reaction-based detection of RET fusions provides the best strategy given its sensitivity, efficiency, cost-effectiveness, minimal error rate, and shorter turnaround time. Batra et al. reported that all the RET fusion-positive patients in their study were non-smokers. This is a remarkable aspect of the study as these findings are in agreement with those reported by previous studies. In addition, the patients with RET fusions had metastases at the time of diagnosis. Therefore, it would be interesting to know if RET fusions are predictive biomarkers for disease progression and metastases. The association between RET fusions and age could not be established as only five patients in this study had RET fusions; moreover, the patients' ages were widely distributed. Therefore, more studies are warranted to determine the potential predictive value of RET fusions associated with a particular age group. Out of the four patients who survived, only one received therapy with a RET inhibitor and RET fusion treatment. It would be interesting to know the difference between these treatments and whether there would be significant difference in prognosis. Further, whether the use of RET inhibitors depends on the tumor proportion score of PD-L1 is not clear. Larger studies on patients with RET-rearranged tumors (non-small-cell lung cancer [NSCLC] and other) are warranted, as recent studies with selpercatinib have shown promising results with durable efficacy in NSCLC (2%–3% RET fusion) and thyroid cancers (70% RET fusions in medullary thyroid cancers) and intracranial activity with minimum or low-grade toxicity, depending on the number of previous lines of treatment; drug-related adverse effects were seen in only 2% of the patients., Selpercatinib is the first drug that targets RET fusion with a durable response to receive an accelerated approval from the United States Food and Drug Administration.,,, However, further studies are warranted to confirm that the treatment provides clinical benefits to patients, such as durable progression-free survival. Therefore, it is important to assess the survival benefit of selpercatinib in patients with RET fusion-positive tumors using the Kaplan–Meier survival analysis.,, A study should be initiated to profile the gene expression and mutation signatures in combination with the RET fusion-positive tumors treated with selpercatinib to derive a molecular signature (panel-mutated genes and differentially expressed genes) associated with fusion and the impact on survival following selpercatinib treatment. This will serve as a good catalog which can guide oncologists and pathologists. In addition, the molecular signature of patients with RET fusion-negative tumors needs to be determined to assess their respective prognosis and survival outcomes. A Pan-India consortium could be launched involving all the cancer institutes and the All India Institute of Medical Sciences using the advancement of NGS technology to comprehensively understand the molecular profiles and patient outcomes (end point of survival with respective chemotherapy). This will help clarify the chemotherapy choices as was done in the MJL Ligtenberg 2020 Dutch study report.
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| References|| |
Batra U, Sharma M, Nathany S, Soni S, Bansal A, Jain P, et al
. Biomarker testing in non-small cell lung carcinoma – More is better: A case series. Cancer Res Stat Treat 2020;3:742-7. [Full text]
Gautschi O, Milia J, Filleron T, Wolf J, Carbone DP, Owen D, et al
. Targeting RET in patients With RET-rearranged lung cancers: Results from the global, multicenter RET registry. J Clin Oncol 2017;35:1403-10.
Drilon A, Oxnard GR, Tan DS, Loong HH, Johnson M, Gainor J, et al
. Efficacy of selpercatinib in RET fusion-positive non-small-cell lung cancer. N Engl J Med 2020;383:813-24.
Wirth LJ, Sherman E, Robinson B, Solomon B, Kang H, Lorch J, et al
. Efficacy of selpercatinib in RET-altered thyroid cancers. N Engl J Med 2020;383:825-35.
Markham A. Selpercatinib: First approval. Drugs 2020;80:1119-24.
Kurzrock R. Selpercatinib aimed at RET-altered cancers. N Engl J Med 2020;383:868-9.
Bradford D, Larkins E, Mushti SL, Rodriguez L, Skinner AM, Helms WS, et al
. FDA approval summary: Selpercatinib for the treatment of lung and thyroid cancers with RET gene mutations or fusions. Clin Cancer Res 2020. doi: 10.1158/1078-0432.CCR-20-3558. Epub ahead of print.
Chakraborty S. A step-wise guide to performing survival analysis. Cancer Res Stat Treat 2018;1:41-5. [Full text]
Rich JT, Neely JG, Paniello RC, Voelker CC, Nussenbaum B, Wang EW. A practical guide to understanding Kaplan-Meier curves. Otolaryngol Head Neck Surg 2010;143:331-6.
Damuzzo V, Agnoletto L, Leonardi L, Chiumente M, Mengato D, Messori A. Analysis of survival curves: Statistical methods accounting for the presence of long-term survivors. Front Oncol 2019;9:453.
van den Broek D, Hiltermann TJ, Biesma B, Dinjens WN, 't Hart NA, Hinrichs JW, et al
. Implementation of novel molecular biomarkers for non-small cell lung cancer in The Netherlands: How to deal with increasing complexity. Front Oncol 2019;9:1521.