The following is the summary of  “Small-Cell Lung Cancer Transformation as a Mechanism of Resistance to Pralsetinib in RET-Rearranged Lung Adenocarcinoma: A Case Report” published in the January 2023 issue of Clinical Lung Cancer by Gazeu, et al.

 The bulk of resistance to Rearranged during transfection (RET)-specific tyrosine kinase inhibitors (TKI) identified in patients with RET-rearranged non-small cell lung cancer (NSCLC) is due to mechanisms that are independent of RET. The phrase “rearranged while transfecting” is what the letters RET stand for when they are abbreviated. Researchers provide the first case report of a RET-rearranged lung adenocarcinoma (LUAD) that changed into small-cell lung cancer. 

This transformation was the mechanism by which the patient developed acquired resistance to pralsetinib (SCLC). In a patient who was 43 years old and had pleural effusion, a RET rearrangement was found in the LUAD gene. This patient also had a RET rearrangement. Following a response to the pralsetinib treatment that lasted for 14 months, a phenotypic change in SCLC was identified through a biopsy of a developing pleural lesion. This was done after the patient had experienced a response to the medication that lasted for 14 months. According to the findings of the molecular study, the primary adenocarcinoma as well as the recurrence were found to contain the same RET fusion and TP53 mutation. This was the case for both of the cancers. 

The chemotherapy treatment with carboplatin and etoposide elicited a partial response from the patient; nonetheless, the patient presented with a worsening condition after six months. It is probable that a histological alteration is a mechanism of resistance to RET-TKIs; as a result, rebiopsy ought to be examined in order to modify the subsequent treatment.