^
23h
New P2 trial • Minimal residual disease • Circulating tumor DNA • Metastases
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KRAS (KRAS proto-oncogene GTPase)
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Imfinzi (durvalumab) • Lumakras (sotorasib)
23h
New P1 trial • Combination therapy • Metastases
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Keytruda (pembrolizumab) • carboplatin • paclitaxel • Lumakras (sotorasib) • pemetrexed • AMG 193
1d
Prospective virtual screening combined with bio-molecular simulation enabled identification of new inhibitors for the KRAS drug target. (PubMed, BMC Chem)
The sotorasib and adagrasib are the recently approved drugs that selectively target KRASG12C, and offer new treatment approaches to enhance patient outcomes however drug resistance frequently arises. These new hits have the potential to inhibit KRASG12C and may help to prevent KRAS-associated lung cancer. All the datasets used in this study can be freely available at ( https://github.com/Amar-Ajmal/Datasets-for-KRAS ).
Journal
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • KRAS G12C
|
Lumakras (sotorasib) • Krazati (adagrasib)
6d
AMG 510 Ethnic Sensitivity Study (CodeBreaK 105). (clinicaltrials.gov)
P1, N=12, Active, not recruiting, Amgen | Trial completion date: Mar 2023 --> Jul 2024
Trial completion date • Metastases
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation • KRAS G12C • KRAS G12
|
Lumakras (sotorasib)
7d
Carfilzomib in Combination With Sotorasib for the Treatment of Patients With KRAS G12C Mutated Advanced or Metastatic Non-small Cell Lung Cancer (clinicaltrials.gov)
P1, N=15, Recruiting, City of Hope Medical Center | Not yet recruiting --> Recruiting | Trial completion date: Apr 2025 --> Mar 2026 | Trial primary completion date: Apr 2025 --> Mar 2026
Enrollment open • Trial completion date • Trial primary completion date • Combination therapy • Metastases
|
KRAS (KRAS proto-oncogene GTPase)
|
Lumakras (sotorasib) • carfilzomib
7d
Hepatotoxicity in patients with non-small cell lung cancer treated with sotorasib after prior immunotherapy: a comprehensive clinical and pharmacokinetic analysis. (PubMed, EBioMedicine)
In this preliminary prospective study, sotorasib after PD-(L)1 blockade was associated with severe hepatotoxicity, especially in patients with a short interval between treatments, prior immune-related hepatitis and higher anti-PD-1 plasma concentrations. Our results suggest a minimum interval of 6 weeks between anti-PD-(L)1 and sotorasib to minimize the risk of hepatotoxicity.
PK/PD data • Journal • PD(L)-1 Biomarker • IO biomarker
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation • KRAS G12C • KRAS G12
|
Keytruda (pembrolizumab) • Lumakras (sotorasib)
10d
ROSIE: Rivaroxaban Sotorasib Interaction Study (clinicaltrials.gov)
P4, N=22, Recruiting, Radboud University Medical Center
New P4 trial
|
Lumakras (sotorasib)
13d
Structural insights into non-hotspot KRAS mutations and their potential as targets for effective cancer therapies. (PubMed, J Biomol Struct Dyn)
We further test whether FDA-approved KRAS inhibitors sotorasib and adagrasib successfully inhibit the E31D and E63K mutants. Based on sharp coherence in trajectories between wild KRAS and non-hotspot mutants, it is suggested that these novel mutants do not contribute to drug resistance mechanism. Overall, we provide a comprehensive understanding of the impact of non-hotspot mutations on KRAS and their potential as targets for effective cancer therapies.Communicated by Ramaswamy H. Sarma.
Journal
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation • KRAS G12C • KRAS G12D • RAS wild-type • KRAS G12 • KRAS Q61H
|
Lumakras (sotorasib) • Krazati (adagrasib)
21d
Twelve-month progression-free survival with sotorasib and panitumumab in KRAS G12C mutant metastatic colorectal cancer. (PubMed, Anticancer Drugs)
Promising inhibitors such as sotorasib and adagrasib targeting KRASG12C mutations have demonstrated efficacy...Treatment with FOLFIRINOX and bevacizumab, and later FOLFIRI and bevacizumab, with surgeries and local interventions resulted in partial responses...This case highlights the remarkable outcome of a heavily treated KRAS G12C mutant mCRC patient. The combination of sotorasib and panitumumab, along with multidisciplinary approaches including surgery and local interventions, played an important role in our patient's survival.
Journal • Metastases
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation • KRAS G12C • KRAS G12
|
Avastin (bevacizumab) • 5-fluorouracil • Vectibix (panitumumab) • Lumakras (sotorasib) • irinotecan • Krazati (adagrasib) • leucovorin calcium
22d
Management of KRAS-mutated non-small cell lung cancer. (PubMed, Clin Adv Hematol Oncol)
With the recent development and approval of selective KRAS G12C inhibitors such as sotorasib and adagrasib for the treatment of advanced or metastatic NSCLC in the second-line setting and beyond, the standard of care for managing these tumors has undergone a significant change. New-generation inhibitors and different combination strategies are being developed in early-phase trials to overcome or delay the onset of resistance as well as to target non-G12C mutations. Owing to the biological heterogeneity of KRAS-mutant NSCLC, treatment will likely need to be individualized based on factors such as co-occurring mutations.
Review • Journal
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation
|
Lumakras (sotorasib) • Krazati (adagrasib)
22d
Strain-release alkylation of Asp12 enables mutant selective targeting of K-Ras-G12D. (PubMed, Nat Chem Biol)
The recently approved non-small cell lung cancer drugs sotorasib and adagrasib covalently capture an acquired cysteine in K-Ras-G12C mutation and lock it in a signaling-incompetent state. Structural insights from X-ray crystallography and exploitation of the stereoelectronic requirements for attack of the electrophile allowed development of a substituted malolactone that resisted attack by aqueous buffer but rapidly crosslinked with the aspartate-12 of K-Ras in both GDP and GTP state. The GTP-state targeting allowed effective suppression of downstream signaling, and selective inhibition of K-Ras-G12D-driven cancer cell proliferation in vitro and xenograft growth in mice.
Journal
|
KRAS (KRAS proto-oncogene GTPase) • RAS (Rat Sarcoma Virus)
|
KRAS mutation • KRAS G12C • KRAS G12D • RAS mutation • KRAS G12
|
Lumakras (sotorasib) • Krazati (adagrasib)
28d
Effect of Strong CYP3A4 Inhibition, CYP3A4 Induction, and OATP1B1/3 Inhibition on the Pharmacokinetics of a Single Oral Dose of Sotorasib. (PubMed, Clin Pharmacol Drug Dev)
The impact of CYP3A4 inhibition was interrogated utilizing repeat doses of 200 mg of itraconazole, a strong CYP3A4 inhibitor, on 360 mg of sotorasib PKs. The impact of CYP3A4 induction was interrogated utilizing multiple doses of 600 mg of rifampin, a strong CYP3A4 inducer...OATP1B1/3 inhibition decreased sotorasib Cmax and AUCinf by 16% and 23%, respectively. These results support that sotorasib can be given together with strong CYP3A4 and OATP1B1/3 inhibitors but the co-administration of sotorasib and strong CYP3A4 inducers should be avoided.
PK/PD data • Journal
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS G12C • KRAS G12
|
Lumakras (sotorasib) • itraconazole • rifampicin
1m
A pair of primary colorectal cancer-derived and corresponding synchronous liver metastasis-derived organoid cell lines. (PubMed, Aging (Albany NY))
IC50 assays confirmed that both cell lines were sensitive to 5-fluorouracil, oxaliplatin, SN-38, and sotorasib. The corresponding adherent cultured CWH22-2D/CLM22-2D cells were established and compared with commonly used CRC cell lines from the ATCC. Both organoids are publicly available to all researchers and will be useful tools for specific human CRC/CLM studies both in vitro and in vivo.
Preclinical • Journal
|
KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • SMAD4 (SMAD family member 4) • KMT2C (Lysine Methyltransferase 2C) • APC (APC Regulator Of WNT Signaling Pathway) • CDKN1B (Cyclin dependent kinase inhibitor 1B) • CA 19-9 (Cancer antigen 19-9)
|
TP53 mutation • KRAS mutation • PIK3CA mutation • TP53 wild-type • APC mutation • SMAD4 mutation
|
5-fluorouracil • Lumakras (sotorasib) • oxaliplatin
1m
Adeno-to-squamous transition drives resistance to KRAS inhibition in LKB1 mutant lung cancer. (PubMed, Cancer Cell)
KRASG12C inhibitors (adagrasib and sotorasib) have shown clinical promise in targeting KRASG12C-mutated lung cancers; however, most patients eventually develop resistance. Notably, expression of the AST plasticity signature and KRT6A at baseline correlates with poor adagrasib responses. These data indicate the role of AST in KRAS inhibitor resistance and provide predictive biomarkers for KRAS-targeted therapies in lung cancer.
Journal
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KRAS (KRAS proto-oncogene GTPase) • STK11 (Serine/threonine kinase 11) • KRT6A (Keratin 6A)
|
KRAS mutation • KRAS G12D • STK11 mutation
|
Lumakras (sotorasib) • Krazati (adagrasib)
1m
Small-molecule inhibition of MAP2K4 is synergistic with RAS inhibitors in KRAS-mutant cancers. (PubMed, Proc Natl Acad Sci U S A)
We find that the combination of sotorasib, a drug targeting KRASG12C, and the MAP2K4 inhibitor HRX-0233 prevents this feedback activation and is highly synergistic in a panel of KRASG12C-mutant lung and colon cancer cells. Moreover, combining HRX-0233 and sotorasib is well-tolerated and resulted in durable tumor shrinkage in mouse xenografts of human lung cancer cells, suggesting a therapeutic strategy for KRAS-driven cancers.
Journal
|
KRAS (KRAS proto-oncogene GTPase) • MAP2K4 (Mitogen-Activated Protein Kinase Kinase 4)
|
KRAS mutation • KRAS G12C
|
Lumakras (sotorasib)
1m
Abnormalities in the KRAS Gene and Treatment Options for NSCLC Patients with the G12C Mutation in This Gene-A Literature Review and Single-Center Experience. (PubMed, Biomedicines)
Two KRAS inhibitors, sotorasib and adagrasib, have recently been approved for the treatment of patients with advanced non-small cell lung cancer with the KRAS G12C mutation, while studies on their efficacy are still ongoing. In this work, we comprehensively analyzed RAS gene mutations' molecular background, mutation testing, KRAS inhibitors' effectiveness with an emphasis on non-small cell lung cancer, the impact of KRAS mutations on immunotherapy outcomes, and drug resistance problems. We also summarized ongoing trials and analyzed emerging perspectives on targeting KRAS in cancer patients.
Review • Journal • IO biomarker
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KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation • KRAS G12C • RAS mutation • KRAS G12
|
Lumakras (sotorasib) • Krazati (adagrasib)
1m
Sotorasib in KRAS G12C-mutated non-small cell lung cancer: A multicenter real-world experience from the compassionate use program in Germany. (PubMed, Eur J Cancer)
First results from a real-world population confirm promising efficacy of sotorasib for the treatment of advanced KRAS p.G12C-mutated NSCLC. Patients with co-occurring KEAP1 mutations seem to derive less benefit.
Journal • Real-world evidence • PD(L)-1 Biomarker • IO biomarker • Real-world
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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 • KRAS G12C • STK11 mutation • KEAP1 mutation • KRAS G12 • KRAS G12C + PD-L1 expression
|
Lumakras (sotorasib)
1m
RAMP 203: Phase 1/2 Study of Avutometinib (VS-6766) + Sotorasib With or Without Defactinib in KRAS G12C NSCLC Patients (clinicaltrials.gov)
P1/2, N=153, Recruiting, Verastem, Inc. | N=53 --> 153 | Trial completion date: Sep 2025 --> Apr 2027
Enrollment change • Trial completion date • Combination therapy
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation • KRAS G12C • KRAS G12
|
Lumakras (sotorasib) • avutometinib (VS-6766) • defactinib (VS-6063)
1m
New P3 trial • Metastases
|
Avastin (bevacizumab) • 5-fluorouracil • Vectibix (panitumumab) • Lumakras (sotorasib) • irinotecan • leucovorin calcium • Mvasi (bevacizumab-awwb)
1m
Application of plasma circulating KRAS mutations as a predictive biomarker for targeted treatment of pancreatic cancer. (PubMed, Cancer Sci)
Sotorasib showed selective inhibition in vitro and in vivo with altered tumor microenvironment, including fibroblasts and macrophages. Collectively, screening for KRAS single mutations in plasma ctDNA and the use of preclinical models of PDO and PDX with genetic mutations would impact precision medicine in the context of PDAC.
Journal
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KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation • KRAS G12D • KRAS G12V • KRAS G12A • KRAS G12S
|
Lumakras (sotorasib)
2ms
Bioinformatics and Experimental Validation for Identifying Biomarkers Associated with AMG510 (Sotorasib) Resistance in KRASG12C-Mutated Lung Adenocarcinoma. (PubMed, Int J Mol Sci)
The findings indicate that these newly identified biomarkers are linked to the abnormal expression of PDL1 and have the potential to induce resistance through immunosuppression. These results highlight the need for further research and therapeutic intervention to address this issue effectively.
Journal • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • HMGA2 (High mobility group AT-hook 2) • SLC2A1 (Solute Carrier Family 2 Member 1)
|
PD-L1 expression • KRAS mutation • KRAS G12C • KRAS G12
|
Lumakras (sotorasib)
2ms
New P1 trial
|
KRAS (KRAS proto-oncogene GTPase)
|
Lumakras (sotorasib) • carfilzomib
2ms
A Potent SOS1 PROTAC Degrader with Synergistic Efficacy in Combination with KRASG12C Inhibitor. (PubMed, J Med Chem)
Importantly, the combination of 23 with AMG510 suppressed RAS signaling feedback activation, showing synergistic effects against KRASG12C mutant cells in vitro and in vivo. Our findings demonstrated that KRASG12C inhibition plus SOS1 degradation as a potential therapeutic strategy to improve antitumor response and overcome acquired resistance to KRASG12C inhibitor.
Journal • Combination therapy
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation
|
Lumakras (sotorasib)
2ms
Enrollment open
|
HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase)
|
Vectibix (panitumumab) • Lumakras (sotorasib)
2ms
Research progress on small molecule inhibitors targeting KRAS G12C with acrylamide structure and the strategies for solving KRAS inhibitor resistance. (PubMed, Bioorg Med Chem)
The development of KRAS G12C mutant conformational modulators and the introduction of Sotorasib (R&D code: AMG510) have been a breakthrough in this field, with its remarkable clinical outcomes...This review classifies KRAS G12C inhibitors based on their chemical structure and evaluates their biological properties. Additionally, it discusses the obstacles encountered in KRAS inhibitor research and the corresponding solutions.
Review • Journal
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation • KRAS G12C
|
Lumakras (sotorasib)
2ms
Farnesyl-transferase inhibitors show synergistic anticancer effects in combination with novel KRAS-G12C inhibitors. (PubMed, Br J Cancer)
Our findings warrant the clinical exploration of KRAS-G12C inhibitors in combination with farnesyl-transferase inhibitors.
Journal • Combination therapy
|
KRAS (KRAS proto-oncogene GTPase) • HRAS (Harvey rat sarcoma viral oncogene homolog) • RHEB (Ras Homolog, MTORC1 Binding)
|
KRAS mutation • HRAS G12C
|
Lumakras (sotorasib) • Zarnestra (tipifarnib)
2ms
New P2 trial • Combination therapy • Metastases
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation
|
Lumakras (sotorasib) • JAB-3312
2ms
Multiple medicinal chemistry strategies of targeting KRAS: State-of-the art and future directions. (PubMed, Bioorg Chem)
To date, the FDA has approved two KRAS inhibitors, sotorasib and adagrasib, for the treatment of patients with KRAS-driven cancers. We systematically summarize recent advances in the discovery and optimization processes of direct KRAS inhibitors (including KRAS, KRAS, KRAS and KRAS inhibitors), indirect KRAS inhibitors (SOS1 and SHP2 inhibitors), pan-KRAS inhibitors, as well as proteolysis-targetingchimeras degrades and molecular chaperone modulators from the perspective of medicinal chemistry. We also discuss the current challenges and opportunities of KRAS inhibition and hope to shed light on future KRAS drug discovery.
Review • Journal
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation
|
Lumakras (sotorasib) • Krazati (adagrasib)
2ms
Discovery of 1H-pyrazolo[3,4-b]pyrazine derivatives as selective allosteric inhibitor of protein tyrosine phosphatase SHP2 for the treatment of KRAS-mutant non-small cell lung cancer. (PubMed, J Biomol Struct Dyn)
In this study, we used the previously reported SHP2 allosteric inhibitor IACS-13909 as a lead drug for structural derivation and modification, and synthesized three SHP2 inhibitors...Furthermore, the combination therapy of compound 4b and KRAS inhibitor sotorasib would play a strong synergistic effect against NCI-H358 cells...Molecular docking study predicted that compound 4b bound to the allosteric site of SHP2 and formed H-bond interactions with key residues Thr108, Glu110, Arg111, and Phe113. In summary, this study aims to provide new ideas for the development of SHP2 allosteric inhibitors for the treatment of KRAS mutant non-small cell lung cancer.Communicated by Ramaswamy H. Sarma.
Journal
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation
|
Lumakras (sotorasib) • BMS-986466
2ms
KRASG12C mutant lung adenocarcinoma: unique biology, novel therapies and new challenges. (PubMed, Pathol Oncol Res)
Furthermore, KRAS mutation affects radiation sensitivity but leads also to bevacizumab and bisphosphonate resistance as well. Similar to other target therapies, clinical administration of KRASG12C inhibitors (sotorasib and adagrasib) resulted in acquired resistance due to various genetic changes not only in KRAS but in other oncogenes as well. Recent clinical studies are aiming to increase the efficacy of G12C inhibitors by novel combination strategies.
Review • Journal
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation • KRAS G12C • KRAS G12
|
Avastin (bevacizumab) • Lumakras (sotorasib) • Krazati (adagrasib)
2ms
Sotorasib is a pan-RASG12C inhibitor capable of driving clinical response in NRASG12C cancers. (PubMed, Cancer Discov)
KRASG12C inhibitors, like sotorasib and adagrasib, potently and selectively inhibit KRASG12C through a covalent interaction with the mutant cysteine, driving clinical efficacy in KRASG12C tumors. Structural and reciprocal mutagenesis studies suggested that differences in isoform-specific binding are mediated by a single amino acid: Histidine-95 in KRAS (Leucine-95 in NRAS). A patient with NRASG12C colorectal cancer treated with sotorasib and the anti-EGFR antibody panitumumab achieved a marked tumor response, demonstrating that sotorasib can be clinically effective in NRASG12C-mutated tumors.
Journal
|
KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog)
|
KRAS mutation • NRAS mutation • NRAS G12 • HRAS G12C • NRAS G12C
|
Vectibix (panitumumab) • Lumakras (sotorasib) • Krazati (adagrasib)
2ms
Tarlox and Sotorasib in Patients With KRAS G12C Mutations (clinicaltrials.gov)
P1/2, N=5, Terminated, Medical University of South Carolina | Active, not recruiting --> Terminated; Study drug was discontinued by manufacturer for business reasons.
Trial termination
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation • KRAS G12C • KRAS G12
|
Lumakras (sotorasib) • Tarlox (tarloxotinib bromide)
2ms
In situ modeling of acquired resistance to RTK/RAS-pathway-targeted therapies. (PubMed, iScience)
Using osimertinib resistance in EGFR-mutated lung adenocarcinoma (LUAD) as a model system, we show that acquired osimertinib resistance can be significantly delayed by inhibition of proximal RTK signaling using SHP2 inhibitors. We additionally modeled resistance to targeted therapies including the KRAS inhibitors adagrasib and sotorasib, the MEK inhibitor trametinib, and the farnesyl transferase inhibitor tipifarnib. These studies highlight the tractability of in situ resistance assays to model acquired resistance to targeted therapies and provide a framework for assessing the extent to which synergistic drug combinations can target acquired drug resistance.
Preclinical • Journal
|
EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase)
|
EGFR mutation
|
Mekinist (trametinib) • Tagrisso (osimertinib) • Lumakras (sotorasib) • Zarnestra (tipifarnib) • Krazati (adagrasib)
2ms
Journal
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation
|
Lumakras (sotorasib)
2ms
Journal
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation
|
Lumakras (sotorasib)
3ms
Ganoderma microsporum immunomodulatory protein combined with KRAS inhibitor impedes intracellular AKT/ERK network to suppress lung cancer cells with KRAS mutation. (PubMed, Int J Biol Macromol)
Combination of GMI and KRAS inhibitor, AMG 510, resulted in more durable inhibition of tumor growth and KRAS activity in H358 cells-xenograft mice. This study highlights the potential of GMI, a dietary fungal protein, as a viable therapeutic avenue for KRAS-mutant lung cancer in combination with KRAS inhibitors.
Journal • Immunomodulating
|
KRAS (KRAS proto-oncogene GTPase) • AVEN (Apoptosis And Caspase Activation Inhibitor)
|
KRAS mutation
|
Lumakras (sotorasib)
3ms
Journal • Metastases
|
KRAS (KRAS proto-oncogene GTPase)
|
Lumakras (sotorasib) • Krazati (adagrasib)
3ms
Tissue factor overexpression promotes resistance to KRAS-G12C inhibition in non-small cell lung cancer. (PubMed, Oncogene)
The recently approved KRAS mutation-specific inhibitors sotorasib and adagrasib (KRAS-I) represent a promising therapy for KRAS-driven non-small cell lung cancer (NSCLC)...Tissue factor (TF) is overexpressed in KRAS-mutated (KRASmut) NSCLC and is the target of the FDA-approved ADC Tivdak...Thus, we have identified the TF/mTORC2 axis as a critical new mechanism for triggering immunosuppression and KRAS-I resistance. We propose that targeting this axis with HuSC1-39 or MTI-31 will improve KRAS-I response in KRAS-driven NSCLC.
Journal
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation • KRAS overexpression
|
Lumakras (sotorasib) • Krazati (adagrasib) • MTI-31 • Tivdak (tisotumab vedotin-tftv)
3ms
1Outcomes Following KRAS Inhibitor Treatment in Patients with KRAS-Mutated Solid Tumors: A Systematic Review and Meta-analysis. (PubMed, Pharmacol Res)
This study provided a comprehensive understanding of the efficacy and safety of KRAS inhibitors in treating solid tumors and identified KEAP1 mutation as a potential predictive biomarker of inferior response in patients treated with KRAS inhibitors. These findings may assist in the design of future clinical trials for identifying populations that may benefit from KRAS inhibitor treatment.
Retrospective data • Review • Journal
|
KRAS (KRAS proto-oncogene GTPase) • KEAP1 (Kelch Like ECH Associated Protein 1)
|
KRAS mutation • KEAP1 mutation
|
Lumakras (sotorasib) • Krazati (adagrasib)
3ms
Mass spectrometry analysis of intact protein N-glycosylation signatures of cells and sera in pancreatic adenocarcinomas. (PubMed, J Zhejiang Univ Sci B)
These results indicated the potential role for tumor-specific glycosylation as disease biomarkers. We also found that AMG-510, a small molecule inhibitor against Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutation, profoundly reduced the glycosylation level in MIA PaCa-2 cells, suggesting that KRAS plays a role in the cellular glycosylation process, and thus glycosylation inhibition contributes to the anti-tumor effect of AMG-510.
Journal
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation • KRAS G12C • KRAS G12
|
Lumakras (sotorasib)
3ms
Sotorasib with panitumumab in chemotherapy-refractory KRAS-mutated colorectal cancer: a phase 1b trial. (PubMed, Nat Med)
Sotorasib-panitumumab demonstrated acceptable safety with promising efficacy in chemotherapy-refractory KRAS-mutated metastatic colorectal cancer. ClinicalTrials.gov identifier: NCT04185883 .
P1 data • Journal
|
KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • SMAD4 (SMAD family member 4)
|
KRAS mutation • KRAS G12C • RAS mutation • KRAS G12
|
Vectibix (panitumumab) • Lumakras (sotorasib)
3ms
MODULE 5: HER2 and Other Emerging Biomarkers for Targeted Therapy in mCRC (ASCO-GI 2024)
This activity is supported by educational grants from Natera Inc and Pfizer Inc. Frequency and clinical relevance of HER2 aberrations among patients with mCRC Published data from the pivotal Phase II MOUNTAINEER trial evaluating tucatinib/trastuzumab for previously treated HER2-positive mCRC; recent FDA approval and optimal incorporation into practice Available efficacy and safety findings with trastuzumab deruxtecan (T-DXd) for patients with HER2-expressing mCRC (eg, from the DESTINY-CRC01 and DESTINY-CRC02 trials); current and potential nonresearch role Incidence of KRAS G12C mutations in patients with mCRC; early data with sotorasib and adagrasib monotherapy Biological rationale for combining KRAS G12C inhibitors with EGFR antibodies Recently presented results from the Phase III CodeBreaK 300 study evaluating sotorasib with panitumumab versus standard therapy for chemorefractory mCRC with KRAS G12C mutations; implications for clinical practice Early data with and ongoing evaluations of other targeted strategies for mCRC
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase)
|
HER-2 positive • KRAS mutation • HER-2 expression
|
Vectibix (panitumumab) • Enhertu (fam-trastuzumab deruxtecan-nxki) • Lumakras (sotorasib) • Tukysa (tucatinib) • Krazati (adagrasib)