News - KEAP1 mutation

17h

Genomic Determinants and an Exploratory Prognostic Model for Immunotherapy Outcomes in Recurrent or Metastatic Cervical Cancer. (PubMed, Oncologist)

Specific genomic alterations may help stratify immunotherapy outcomes in recurrent or metastatic cervical cancer. The proposed genomic risk model remains exploratory and requires validation in larger, independent cervical cancer cohorts.

17 hours ago

Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • HRD (Homologous Recombination Deficiency) • KEAP1 (Kelch Like ECH Associated Protein 1) • TERT (Telomerase Reverse Transcriptase) • BAP1 (BRCA1 Associated Protein 1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • TNFA (Tumor Necrosis Factor-Alpha) • CREBBP (CREB binding protein) • EP300 (E1A binding protein p300)

TP53 mutation • PIK3CA mutation • KEAP1 mutation

SMARCA4, STK11, and KEAP1 co-inactivation associates with poor prognosis and upregulation of the TGF-β pathway in lung adenocarcinoma. (PubMed, bioRxiv)

RNA-Seq and DNaseI-Seq of these in vitro models and clinical samples identified upregulation of TGF-β signaling and EMT gene expression signatures, and corresponding changes in chromatin accessibility, in SMARCA4/STK11/KEAP1 triple mutant LUAD. We identify SMARCA4/STK11/KEAP1 triple mutant LUAD as a prognostically significant disease subset and nominate TGF-β signaling as a potential therapeutic target.

1 day ago

Journal • IO biomarker

STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • TGFB1 (Transforming Growth Factor Beta 1) • ITK (IL2 Inducible T Cell Kinase)

STK11 mutation • KEAP1 mutation

Targeting KRAS codon 13 mutations using direct combination approaches in non-small cell lung cancer. (PubMed, Cancer Discov)

To determine combination partners that enhance RAS(ON) mutant-selective inhibition, a drug repurposing screen revealed that KRASG13C models are selectively vulnerable to chemotherapy. Combination of docetaxel with RMC-8839 demonstrated robust anti-proliferative activity in KRASG13C-driven NSCLC models in vitro and in vivo.

1 day ago

Journal

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • STK11 (Serine/threonine kinase 11) • NF1 (Neurofibromin 1) • KEAP1 (Kelch Like ECH Associated Protein 1)

KRAS mutation • KRAS G12C • BRAF mutation • STK11 mutation • KRAS G13D • RAS mutation • KEAP1 mutation • KRAS G13

docetaxel

M25RIO: A short treatment with immunotherapy instead of radiotherapy in early-stage lung cancer (2025-524305-32-00)

P1/2, N=30, Not yet recruiting, Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

7 days ago

New P1/2 trial

PD-L1 (Programmed death ligand 1) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1)

STK11 mutation • KEAP1 mutation

Libtayo (cemiplimab-rwlc)

miR-941 in extracellular vesicles confers anlotinib resistance via Keap1/Nrf2 axis and represents a therapeutic target in non-small cell lung cancer. (PubMed, Clin Transl Med)

EV-derived miR-941 as a key driver of anlotinib resistance via the Keap1/Nrf2 pathway represent a promising non-invasive predictive biomarker and a potential therapeutic target for overcoming resistance in NSCLC.

8 days ago

Journal • IO biomarker

BCL2 (B-cell CLL/lymphoma 2) • KEAP1 (Kelch Like ECH Associated Protein 1) • MCL1 (Myeloid cell leukemia 1)

KEAP1 mutation

Focus V (anlotinib)

Curcumin improves bladder dysfunction in diabetic rats by attenuating oxidative stress via the Keap1/NRF2/HO-1 pathway. (PubMed, Transl Androl Urol)

Histological analyses revealed attenuated bladder tissue fibrosis and apoptosis, concomitant with suppressed Keap1 and elevated expression of NRF2, HO-1, and SOD1 in the bladder tissue. Cur alleviates OS and thereby ameliorates DBD in diabetic rats by regulating the Keap1/NRF2/HO-1 pathway, which highlights its therapeutic potential for DBD.

9 days ago

Preclinical • Journal • IO biomarker

BCL2 (B-cell CLL/lymphoma 2) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2) • HMOX1 (Heme Oxygenase 1) • CASP3 (Caspase 3) • SOD1 (Superoxide Dismutase 1)

KEAP1 mutation

12d

Clinicogenomic Landscape of Histologic Subtypes in Ovarian Cancer: Real-World Evidence From a Japanese Nationwide Cohort. (PubMed, JCO Precis Oncol)

This large clinicogenomic study in an Asian population highlights unique mutational landscapes and survival associations, which may inform personalized treatment strategies.

12 days ago

Retrospective data • Journal • HEOR • Real-world evidence • BRCA Biomarker

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • KEAP1 (Kelch Like ECH Associated Protein 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2)

TP53 mutation • KRAS mutation • BRCA2 mutation • PIK3CA mutation • ARID1A mutation • CDKN2A deletion • KEAP1 mutation • NFE2L2 mutation

12d

Peri-Implant Gingival Undifferentiated SWI/SNF Complex-Deficient Tumor with Molecularly Confirmed Biallelic SMARCA4 Inactivation: Diagnostic Pitfalls and Genomic Characterization. (PubMed, Diagnostics (Basel))

The patient initiated carboplatin-paclitaxel and achieved a partial response at one month with further shrinkage by four months. Rapidly enlarging peri-implant gingival masses should prompt timely biopsy and SWI/SNF marker testing when histology is high-grade and lineage-ambiguous. NGS-based molecular profiling confirms diagnosis, elucidates mechanism, and reveals actionable targets in this rare tumor class.

12 days ago

Journal • Tumor mutational burden

TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • KEAP1 (Kelch Like ECH Associated Protein 1) • MTAP (Methylthioadenosine Phosphorylase) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • MAT2A (Methionine Adenosyltransferase 2A)

TP53 mutation • TMB-H • CDKN2A deletion • MTAP deletion • KEAP1 mutation

Oncomine™ Comprehensive Assay Plus

carboplatin • paclitaxel

14d

Molecular and clinical characteristics of patients with non-small cell lung cancer (NSCLC) harboring KRAS Q61 mutations to assess therapeutic responses. (PubMed, Clin Cancer Res)

KRAS Q61H and Q61L were the predominant mutational subtypes and demonstrated distinct molecular and clinical characteristics, with differences in co-mutational landscape and survival differences. Immunotherapy-based regimens were associated with more favorable outcomes compared to chemotherapy, particularly in patients with high PD-L1 expression, underscoring the importance of subtype-specific molecular characterization in clinical decision-making.

14 days ago

Journal • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1)

PD-L1 expression • TP53 mutation • KRAS mutation • PD-L1 overexpression • STK11 mutation • KEAP1 mutation • KRAS Q61

14d

Betaine induces ferroptotic stress by enhancing KEAP1-mediated NRF2 degradation in breast cancer cells. (PubMed, Cell Signal)

BET may promote ferroptosis-associated cell death and suppress breast cancer cell malignant phenotypes, potentially through modulation of the KEAP1/NRF2/xCT/GPX4 pathway. These findings suggest a possible therapeutic relevance of BET in breast cancer, although further in vivo and clinical validation is required.

14 days ago

Journal

KEAP1 (Kelch Like ECH Associated Protein 1) • GPX4 (Glutathione Peroxidase 4)

KEAP1 mutation • NFE2L2 mutation

16d

Targeting NRF2 addiction in cancer: synthetic lethal strategies beyond direct inhibition. (PubMed, Front Cell Dev Biol)

This review focuses on targeting NRF2-driven metabolic dependencies as synthetic lethal vulnerabilities, spanning pathways such as glutaminolysis, redox imbalance, cystine metabolism, nucleotide biosynthesis and ER proteostasis. We also highlight emerging strategies, including allosteric KEAP1 activators, and discuss key challenges in translating these approaches into effective therapies.

16 days ago

Review • Journal

KEAP1 (Kelch Like ECH Associated Protein 1) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2)

KEAP1 mutation • NFE2L2 mutation

22d

IACS-6274 With or Without Bevacizumab and Paclitaxel for the Treatment of Advanced Solid Tumors (clinicaltrials.gov)

P1, N=54, Recruiting, M.D. Anderson Cancer Center | Trial completion date: May 2026 --> Jun 2028 | Trial primary completion date: May 2026 --> Mar 2028

22 days ago

Trial completion date • Trial primary completion date

PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • ARID1A (AT-rich interaction domain 1A) • NF1 (Neurofibromin 1) • KEAP1 (Kelch Like ECH Associated Protein 1) • PD-1 (Programmed cell death 1) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2)

PIK3CA mutation • PTEN mutation • ARID1A mutation • STK11 mutation • KEAP1 mutation • NFE2L2 mutation

Avastin (bevacizumab) • paclitaxel • Truqap (capivasertib) • IPN60090