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Ref Type Journal Article
PMID (33832284)
Authors Long Y, Tang Y, Cai C, Yu M, Zhang M, Chen R, Huang M
Title The influence of STK11 mutation on acquired resistance to immunotherapy in advanced non-small cell lung cancer with Lynch syndrome: a case report and literature review.
Journal Vol Issue Date Pages Journal Short Title
Annals of palliative medicine 10 6 2021 Jun 7088-7094 Ann Palliat Med
URL
Abstract Text Immune checkpoint inhibitors (ICI) monotherapy or combination therapies have become increasingly popular in patients with advanced non-small cell lung cancer (NSCLC). However, there are still many unknowns concerning the predictive bio-markers and resistance mechanisms to immunotherapy. Patients with primary tumor STK11 mutation reportedly to have a lower response rate than the STK11 wild-type and possibly a primary resistance mechanism to ICIs. However, there is presently no data regarding the contribution of STK11 to acquired resistance to ICIs. Herein we report on a patient who was diagnosed with advanced lung squamous cell carcinoma accompanied by Lynch syndrome. The patient developed an STK11 mutation after receiving pembrolizumab as a first-line treatment. Programmed death ligand 1 (PD-L1) was highly expressed (50%) in the biopsy. HRAS Q61L and TP53 R158L were mainly detected. Unexpectedly, the patient carried an MSH6 heterozygous germline mutation, and was classified as proficient mismatch repair (pMMR). The patient subsequently received pembrolizumab (200 mg, ivgtt, q3w) as first line therapy and achieved stable disease (SD) as the best response. After eight treatment cycles, the patient suffered disease progression (PD), and an STK11 frameshift mutation was newly identified in his plasma circulating tumor deoxyribonucleic acid (ctDNA). This case study suggests that STK11 could contribute to pembrolizumab acquired resistance. Furthermore, the patient was also diagnosed with Lynch syndrome, which rarely occurs in lung cancer.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
CD274 over exp STK11 A205Rfs*82 lung squamous cell carcinoma predicted - resistant Pembrolizumab Case Reports/Case Series Actionable In a clinical case study, a lung squamous cell carcinoma patient with high CD274 (PD-L1) expression progressed after initial response to Keytruda (pembrolizumab) and through subsequent ctDNA testing was found to have acquired STK11 A205Rfs*82 (PMID: 33832284). 33832284