Targeting TROP-2 in treatment-resistant non-small cell lung cancer harboring the G12C mutation and TROP-2 upregulation: A case report.

Non-small cell lung cancer (NSCLC) with v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog gene () mutations is one of the most aggressive and refractory tumors. Trophoblast cell-surface antigen 2 (TROP-2) is a recognized marker of poor prognosis in NSCLC. Several clinical trials targeting TROP-2 and mutations have established novel possibilities for the treatment of patients with NSCLC. However, the results remain unsatisfactory, likely due to the heterogeneity of tumor cells and the presence of diverse co-mutations. No consensus has been reached regarding the treatment of patients with concurrent TROP-2 upregulation and mutations. The present report describes the case of a patient diagnosed with lung adenocarcinoma who presented with a G12C mutation, TROP-2 upregulation and widespread treatment-resistant disease. The patient subsequently benefited from a novel antibody-drug conjugate targeting human TROP-2 as second-line treatment following first lines of therapy. Follow-up computed tomography imaging over a 34-month treatment period demonstrated partial remission (42% reduction based on Response Evaluation Criteria in Solid Tumors version 1.1) without serious adverse events. Currently, therapeutic options for patients with recurrent NSCLC exhibiting simultaneous TROP-2 upregulation and mutation are limited. Targeting TROP-2 may represent a novel therapeutic approach for patients with NSCLC, particularly those with chemo-radioresistant disease.