Introduction: The Non-Small Cell Lung Cancer (NSCLC) with rare genomic alterations poses a significant clinical challenge due to a lack of established therapeutic guidelines. Case Presentation: We report the application of a precision medicine strategy integrating genomic profiling with in silico molecular docking to guide therapy for two patients harboring such rare mutations. Genomic analysis identified a rare EGFR exon 18/20 insertion in one patient and a resistant ALK C1156Y mutation in another. Selection of the appropriate drug was carried out using molecular docking simulations, which predicted high binding affinity of the irreversible EGFR inhibitor afatinib for the unique EGFR insertion and of the ALK inhibitor alectinib for the C1156Y-mutated kinase. We observed that the computationally-informed choices of afatinib and alectinib subsequently led to notable clinical and radiological improvements in the respective patients. Conclusion: The association between the docking predictions and clinical outcomes corroborates the utility of computational modeling for tailoring therapies, although the structural models provide mechanistic insight into drug efficacy against these rare mutations. The present integrated approach emphasizes the value of merging in silico methods into clinical decision-making to overcome the therapeutic uncertainty of uncommon oncogenic driver alterations.
Gafoor et al. (Tue,) studied this question.