Identification of a KRAS mutation in a patient with non-small cell lung cancer treated with chemoradiotherapy and panitumumab

Figures & data

Figure 1. A PET-CT showed avidity in the lung mass (A). Bronchoscopic biopsy with subsequent DNA Sanger sequencing (B) identified a minor clone containing an activating, KRAS G12D mutation. A PET/CT after completion of radiation, chemotherapy, and panitumumab showed a partial response with reduced FDG uptake and residual disease in the mediastinum (C). Ion torrent sequencing revealed that the residual tumor cells harbor the same cancer gene mutations as the pretreatment tumor tissues, with the exception of G12D KRAS mutation being absent (D). In mCRC, which are predominantly adenocarcinomas, panitumumab halts the phosphorylation of KRAS-GDP, preventing activation of the KRAS/RAF/MEK/ERK pathway ([E], blocked pathways grayed out); however, activating mutations cause constitutive activation of the downstream pathway ([F], pathway no longer gray). In NSCLC, even when an activating KRAS mutation is present, all pathways contribute to cell cycle progression, proliferation, angiogenesis, metastasis, and production of EGFR ligands that cause radioresistance ([G], without panitumumab all pathways are active); with panitumumab, although the KRAS pathways may be constitutively activated, the overall number of effectors contributing to cancer cell proliferation is decreased ([H], panitumumab causes inactivation of pathways, now grayed out).