Concurrent Mutations in STK11 and KEAP1 Cause Treatment Resistance in KRAS Wild-type Non-small-cell Lung Cancer

Masahiko Sumii; Masashi Namba; Kentaro Tokumo; Masami Yamauchi; Wataru Okamoto; Noboru Hattori; Kazuhiko Sugiyama

doi:10.2169/internalmedicine.1110-22

Concurrent Mutations in STK11 and KEAP1 Cause Treatment Resistance in KRAS Wild-type Non-small-cell Lung Cancer

Intern Med. 2023 Oct 15;62(20):3001-3004. doi: 10.2169/internalmedicine.1110-22. Epub 2023 Mar 1.

Authors

Masahiko Sumii¹, Masashi Namba², Kentaro Tokumo², Masami Yamauchi², Wataru Okamoto³, Noboru Hattori¹, Kazuhiko Sugiyama^{2

3}

Affiliations

¹ Department of Respiratory Medicine, Hiroshima University Hospital, Japan.
² Department of Clinical Oncology, Hiroshima University Hospital, Japan.
³ Department of Cancer Treatment Center, Hiroshima University Hospital, Japan.

Abstract

We herein report a patient with KRAS wild-type non-small-cell lung cancer (NSCLC) with concurrent STK11 and KEAP1 mutations. A 53-year-old man visited a local doctor with a complaint of left shoulder swelling and pain. He was diagnosed with NSCLC cT4N0M1c stage IVB. A comprehensive genome profile test revealed mutations in STK11 and KEAP1 but no KRAS mutations. The patient was refractory to radiotherapy, immunotherapy, and chemotherapy. Thus, STK11 and KEAP1 mutations can be considered resistance mutations that confer resistance to various anticancer therapies in KRAS wild-type NSCLC.

Keywords: CGP test; KEAP1 mutation; KRAS mutation; STK11 mutation; non-small-cell lung cancer (NSCLC); therapy resistance.

Publication types

Case Reports

MeSH terms

AMP-Activated Protein Kinase Kinases
Carcinoma, Non-Small-Cell Lung* / drug therapy
Carcinoma, Non-Small-Cell Lung* / genetics
Humans
Kelch-Like ECH-Associated Protein 1 / genetics
Lung Neoplasms* / drug therapy
Lung Neoplasms* / genetics
Male
Middle Aged
Mutation / genetics
NF-E2-Related Factor 2 / genetics
NF-E2-Related Factor 2 / therapeutic use
Protein Serine-Threonine Kinases / genetics
Proto-Oncogene Proteins p21(ras) / genetics
Proto-Oncogene Proteins p21(ras) / therapeutic use

Substances

Proto-Oncogene Proteins p21(ras)
Kelch-Like ECH-Associated Protein 1
NF-E2-Related Factor 2
Protein Serine-Threonine Kinases
KRAS protein, human
KEAP1 protein, human
STK11 protein, human
AMP-Activated Protein Kinase Kinases