refametinib (BAY86-9766) / AstraZeneca - LARVOL DELTA

Drug sensitivity patterns across FAB subtypes and molecular mutations in AML. (ASCO 2025) - "M1 samples (n=22 patients) demonstrated higher sensitivity to Navitoclax (σsDSS = 15.89), while combinations with mTOR inhibitors like Navitoclax + PF-04691502 (σsDSS = 13.97) and Navitoclax + Vistusertib (σsDSS = 13.72) showed promise...M4 subtypes (n=2 patients) were most sensitive to BAY 87-2243 (σsDSS = 15.98), with dual combinations like BAY 87-2243 + Cerdulatinib (σsDSS = 14.21) and BAY 87-2243 + Pevonedistat (σsDSS = 14.13) maintaining strong responses...In M4 eos (n=9 patients), Pimasertib demonstrated notable effectiveness (σsDSS = 14.43), with dual-agent combination such as Pimasertib + SCH772984 (σsDSS = 14.24) supporting RAS/ERK pathway inhibition. Despite rare M4/M5 subtypes (n=2 patients) showing limited Refametinib sensitivity (σsDSS = 8.75), their minimal sample size precludes definitive conclusions...Likewise, mutation analysis revealed that NPM1-mutated samples showed increased sensitivity to Venetoclax (σsDSS = 13.28) and PF-04691502 (σsDSS =..."

Acute Myelogenous Leukemia • FLT3 • NPM1

Targeting the phosphatidylinositol-3-kinase (PI3K) and mitogen activated protein kinase (MAPK) signalling pathways to enhance chemoradiotherapy in locally advanced rectal cancer. (PubMed, Cancer Treat Res Commun) - "A panel of colorectal cancer (CRC) cell lines (n = 10) with varying PI3K and MAPK mutational backgrounds were treated with combinations of 5-Flourouracil (5-FU), radiation, the PI3K inhibitor copanlisib, and/or the MEK inhibitor refametinib, and their effects on proliferation in vitro were measured...Our results suggest that activation of the kinase signalling pathway may modulate PI3K/MEK inhibitor responsiveness in colorectal cancer. Furthermore, the addition of copanlisib to 5-FU chemoradiotherapy resulted in an enhanced anti-proliferative cytotoxic effect compared to 5-FU chemoradiotherapy alone, regardless of the background mutational status, and supports further clinical development of this regimen."

Journal • Colorectal Cancer • Oncology • Rectal Cancer • Solid Tumor • KRAS • PIK3CA

Bioinformatics screened of biomarkers for the prognosis of hepatocellular carcinoma. (PubMed, Cancer Biomark) - "Hub genes were enriched in various cell types. Trametinib, selumetinib, RDEA119, and teniposide were identified as potential drugs for LIHC treatment.ConclusionCDC20, TOP2A, CDK1, CAT, TAT, and FTCD may contribute to LIHC development and serve as novel prognostic biomarkers."

Biomarker • Journal • Hepatocellular Cancer • Oncology • Solid Tumor • CDC20 • CDK1 • FTCD • TOP2A

The role of SEC14L4 in esophageal squamous cell cancer: insights into clinical relevance and molecular pathways. (PubMed, Transl Cancer Res) - "Drug sensitivity analysis indicated the association of SEC14L4 expression with sensitivity of ESCC to the common chemotherapy drugs AICAR, BMS.708163, GNF.2, Nutlin.3a, PD.0325901, and RDEA119. Verification of the high expression of SEC14L4 in KYSE520 and KYSE150 was conducted, thereby confirming the study's findings. High expression of SEC14L4 is associated with poorer clinical outcomes, highlighting its potential as a therapeutic target and suggesting its involvement in the molecular mechanisms underlying ESCC."

Journal • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma

Establishment of prognosis model of hepatocellular carcinoma based on prognosis related gene analysis and study on gene regulation mechanism of model. (PubMed, Heliyon) - "In addition, the high expression of model gene produced drug resistance to trametinib, selumetinib and RDEA119 (refametinib). The prognostic risk model based on six prognostic related DEGs is an independent prognostic factor of HCC, which can effectively predict the survival and prognosis of HCC patients."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • BUB1 • CCNA2 • CCNB1 • CDC20 • CDK1 • TOP2A

Phase I-IV Drug Trials on Hepatocellular Carcinoma in Asian Populations: A Systematic Review of Ten Years of Studies. (PubMed, Int J Mol Sci) - "Eighteen studies compared the efficacy of sorafenib with that of other drugs, including lenvatinib, cabozantinib, tepotinib, tigatuzumab, linifanib, erlotinib, resminostat, brivanib, tislelizumab, selumetinib, and refametinib. This study provides comprehensive insights into effective treatment interventions for HCC in Asian populations. The overall assessment indicates that sorafenib, used alone or in combination with atezolizumab and bevacizumab, has been the first treatment choice in the past decade to achieve better outcomes in patients with HCC in Asian populations."

Journal • Review • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • Transplantation

A practical approach to demonstrate the circular economy in remediation of textile dyes using nutraceutical industrial spent. (PubMed, RSC Adv) - "We used Nutraceutical Industrial Coriander Seed Spent (NICSS), a readily available, cheap, eco-friendly, and ready-to-use material, as an innovative adsorbent for the bioremediation of a bisazo Acid Red 119 (AR 119) dye, which is likely a mutagen from textile industrial effluents (TIE)...Utilizing plastic trash, the dye-adsorbed NICSS that was recovered as "sludge" was utilized as a reinforcing material to create composites. Dye-adsorbed NICSS thermoplastic and thermoset composites were studied and compared with NICSS composites in terms of their physicomechanical and chemical properties."

Journal

Comprehensive analysis of CPNE1 predicts prognosis and drug resistance in gastric adenocarcinoma. (PubMed, Am J Transl Res) - "CPNE1 could be a predictive biomarker and a potential target for biological therapy in STAD."

Journal • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CPNE1

DNA hypomethylation patterns and their impact on the tumor microenvironment in colorectal cancer. (PubMed, Cell Oncol (Dordr)) - "This study unveils a novel epigenetic phenotype in CRC linked to resistance against immune checkpoint inhibitors, presenting a significant step toward personalized medicine by suggesting epigenetic classifications as a means to identify ideal candidates for immunotherapy in CRC. Our findings also highlight potential therapeutic agents for the DMP subtype, offering new avenues for tailored CRC treatment strategies."

Biomarker • IO biomarker • Journal • Tumor microenvironment • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

In Silico Identification of Therapeutic Targets and Novel Drug Candidates for Malignant Peripheral Nerve Sheath Tumors. (PubMed, Front Biosci (Landmark Ed)) - "Overall, our results describe the importance of Twist1 in MPNST pathogenesis. Everolimus was also found to be a potential therapeutic drug for MPNSTs."

Journal • Brain Cancer • Fibrosis • Neurofibromatosis • Neurofibrosarcoma • Oncology • Sarcoma • Solid Tumor • TWIST1

Establishment and characterization of human organoids derived from medullary cancer and serrated adencocarcinoma; rare histological variants of colorectal cancer (EACR 2023) - "The ClinXPro-Report revealed a potential sensitivity of the different organoids to drugs such as the ERK1/ERK2 inhibitor Ulixertinib, the PI3K inhibitor Pilaralisib, the MEK inhibitor Refametinib or the S6K1 inhibitor PF-4708671.ConclusionCRC-PDOs can be used as tools to model different histological subtypes of CRC. Notably, the less frequent subtypes SAC and MC exhibited, in our analysis, significantly greater differences in gene expression compared to CCs. Our results suggest that further characterization of less frequent subtypes is necessary and that PDOs can have potential implications in the development of personalized therapies."

Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • KRAS • MAPK1 • NRAS

Identification of a novel circRNA-miRNA-mRNA regulatory axis in hepatocellular carcinoma based on bioinformatics analysis. (PubMed, Sci Rep) - "The results suggest that the sensitivity toward trametinib, refametinib (RDEA119), and selumetinib correlates to the expression of WDR76. ROC analysis showed that the area under the curve (AUC) of all genes in the regulatory axis was greater than 0.7. The identified hsa_circ_0000417/hsa_circ_0002688/hsa_circ_0001387--hsa-miR-199a-5p--WDR76 regulatory axis may provide new insights into the progression, clinical diagnosis, and treatment of HCC."

IO biomarker • Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Immune Modulation • Liver Cancer • Oncology • Solid Tumor • ACTG1 • E2F3 • MIR199A • MIR199A1 • NORE1A

Receptor Tyrosine Kinase dependent PI3K activation is an escape mechanism to vertical suppression of the EGFR/RAS/MAPK pathway in KRAS-mutated colorectal cancer cell lines. (ESMO 2018) - "... We generated four different KRAS mutated CRC cell lines (HCT15, HCT116, LoVo, SW480) resistant to a combination of cetuximab (anti-EGFR antibody) and refametinib (BAY86-9766, selective MEK-inhibitor) after continuous exposure to increasing concentration of the drugs...Either selective knockdown of these RTKs or treatment with the pan-HER inhibitor afatinib (BIBW2992) failed to revert the resistance phenotype in our cellular model, while treatment with pictilisib (GDC-0941, selective PI3Kα inhibitor) was able to restore the sensitivity to the drug combination... Our in vitro preliminary data demonstrate that PI3K activation plays a central role in the acquired resistance to the combination of anti-EGFR and MEK-i in KRAS mutated colorectal cancer cell lines. PI3K activation is achieved through concurrent activation of multiple RTKs such as HER2, HER3 and IGF1R, suggesting a cooperative mechanism."

Preclinical • Colorectal Cancer

Integrated analysis of pivotal biomarker of LSM1, immune cell infiltration and therapeutic drugs in breast cancer. (PubMed, J Cell Mol Med) - "Most importantly, pharmacogenetic analysis of BRCA cell lines revealed that LSM1 inactivation was associated with increased sensitivity to refametinib and trametinib. However, both drugs could mimic the effects of LSM1 inhibition and their drug sensitivity was associated with MEK molecules. Therefore, we investigated the clinical application of LSM1 to provide a basis for sensitive diagnosis, prognosis and targeted treatment of breast cancer."

Biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • BRCA

Integrated analysis of pivotal biomarker, immune cell infiltration, and therapeutic drugs for LSM1-mutated in breast cancer. (ASCO 2022) - "Most importantly, pharmacogenetic analysis of BRCA cell lines revealed that LSM1 inactivation was associated with increased sensitivity to refametinib, and trametinib. In brief, our finding may contribute to increasing currently limited prognostic biomarkers and treatment options for breast cancer."

Biomarker • Breast Cancer • Oncology • Solid Tumor • BRCA

Bioremediation of Textile Industrial Effluents Using Nutraceutical Industrial Spent: Laboratory-Scale Demonstration of Circular Economy. (PubMed, Nanomaterials (Basel)) - "This research reports the first-ever study on abundantly available, environmentally friendly, low-cost and ready-for-use Nutraceutical Industrial Cumin Seed Spent (NICUS) as an innovative adsorbent for bioremediation of a bisazo Acid Red 119 (AR119) dye, a probable mutagen from textile industrial effluents (TIEs)...The physicomechanical and chemical properties of thermoplastic and thermoset composite using dye-adsorbed NICUS were evaluated and compared with NICUS composites. Prospects of integrating Small and Medium Enterprises (SMEs) into the circular economy of Nutraceutical Industrial Spent (NIS) are discussed."

Journal

Establishment of prognostic risk model and drug sensitivity based on prognostic related genes of esophageal cancer. (PubMed, Sci Rep) - "High expression of HIST1H1E was resistant to trametinib, selumetinib, RDEA119, docetaxel and 17-AAG, High expression of UBE2C was resistant to masitinib, and Low expression of ERO1B made the EC more sensitive to FK866. We constructed an EC risk score model composed of 8 DEGs and gene resistance analysis, which can provide reference for prognosis prediction, diagnosis and treatment of the EC patients."

Journal • Esophageal Cancer • Gastrointestinal Cancer • Oncology • APOA2 • ERO1B • UBE2C

MEK 1/2 inhibitors in the treatment of gynecologic malignancies (Gynecol Oncol) - “This paper reviews the translational evidence in favor of MEK inhibitors in cancer, their role in gynecologic malignancies, and details regarding the status of the fourteen MEK inhibitors currently being clinically tested: trametinib, selumetinib, pimasertib, refametinib, PD-0325901, MEK162, TAK733, RO5126766, WX-554, RO4987655, cobimetinib, AZD8330, MSC2015103B, and ARRY-300.” 

Review • Oncology

Statistics and network-based approaches to identify molecular mechanisms that drive the progression of breast cancer. (PubMed, Comput Biol Med) - "Finally, we suggested KGs-guided three repurposable candidate-drugs (Trametinib, selumetinib, and RDEA119) for BC treatment by using the GSCALite online web tool and validated them through molecular docking analysis, and found their strong binding affinities. Therefore, the findings of this study might be useful resources for BC diagnosis, prognosis and therapies."

Journal • Breast Cancer • Oncology • Solid Tumor • BUB1 • CCNA2 • CCNB1

Combination of multifunctional ursolic acid with kinase inhibitors for anti-cancer drug carrier vesicles. (PubMed, Mater Sci Eng C Mater Biol Appl) - "Further on, mono- and combination therapy with UA and six different kinase inhibitors (crizotinib, erlotinib, foretinib, gefitinib, refametinib, trametinib) was tested on seven cancer cell-lines. The coupled intercalation of UA and trametinib (2:1 molar ratio) into vesicles causes further structural advantageous molecular interactions, promoting the formation of small vesicles. The high drug:lipid molar ratio (~0.5) in the novel type of co-delivery vesicles enables their direct medical application, possibly also overcoming the multidrug resistance effect."

Journal • Oncology

SKA3 Serves as a Biomarker for Poor Prognosis in Kidney Renal Papillary Cell Carcinoma. (PubMed, Int J Gen Med) - "In addition, we found that MEK inhibitors, ie, trametinib, selumetinib, PD0325901, and RDEA119, may be feasible targeting agents for KIRP patients. SKA3 might contribute to poor prognosis of KIRP through cell cycle, DNA damage, hormone androgen receptor, hormone estrogen receptor, PI3K/Akt, and RAS/MAPK. SKA3 potentially serves as a prognostic biomarker and target for KIRP."

Biomarker • Journal • Oncology • AR • AURKB • BUB1B • CCNA2 • CCNB1 • CCNB2 • CDC20 • CDK1 • ER • PLK1

Activation of ERK and p38 Reduces AZD8055-Mediated Inhibition of Protein Synthesis in Hepatocellular Carcinoma HepG2 Cell Line. (PubMed, Int J Mol Sci) - "Combined treatment of AZD8055 with the MAPK kinase1/2 (MEK1/2) inhibitor refametinib or the p38 inhibitor SB203580 markedly decreased translation in HepG2 cells. Interestingly, AZD8055 modulated the 4E-BP1 mRNA pool by up-regulating ERK1/2 and p38 pathways. Together, these results suggest that AZD8055-induced activation of MAPKs interferes with inhibition of protein synthesis at an early stage of mTORC1/2 inhibition, and that it may contribute to the development of resistance to mTORC1/2 inhibitors."

Journal • Preclinical • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • EIF4EBP1

Identification of DNA-Repair-Related Five-Gene Signature to Predict Prognosis in Patients with Esophageal Cancer. (PubMed, Pathol Oncol Res) - "We found that small-molecule drugs (trametinib, selumetinib, and refametinib) could help to improve patient survival. In summary, our study provides a novel and promising prognostic signature based on DNA-repair-related genes to predict survival of patients with ESCA. Systematic data mining provides a theoretical basis for further exploring the molecular pathogenesis of ESCA and identifying therapeutic targets."

Clinical • Journal • Esophageal Cancer • Gastrointestinal Cancer • Oncology

Targeting the PI3K and MAPK pathways to improve response to HER2-targeted therapies in HER2-positive gastric cancer. (PubMed, J Transl Med) - "PI3K or MEK inhibition alone or in combination with anti-HER2 therapy may represent an improved treatment strategy for some patients with HER2-positive GC, and warrants further investigation in a clinical trial setting."

Journal • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • EGFR • ERBB3 • ERBB4 • HER-2 • PIK3CA

Allosteric Kinase Inhibitors Reshape MEK1 Kinase Activity Conformations in Cells and In Silico. (PubMed, Biomolecules) - "Application of the allosterically acting MEK inhibitors (MEKi) trametinib, cobimentinib, refametinib, and selumetinib converted activated MEK1 KinCon reporters back into a more closed inactive conformation. We observed increased dynamics for the S218D/S222D double mutant particularly in the region of the distal A-helix and alpha-C helix. These data underline that MEK1 KinCon biosensors have the potential to be subjected to MEKi efficacy validations in an intact cell setting."

Journal • Melanoma • Oncology • Solid Tumor • BRAF • MAP2K1