- |||||||||| Ibrance (palbociclib) / Pfizer, Mekinist (trametinib) / Novartis, BeiGene
Journal: Trametinib boosts palbociclib's efficacy in breast cancer via autophagy inhibition. (Pubmed Central) - Jul 1, 2024
A combination of PAL and TRA synergistically reduced cell viability and proliferation, and in vivo studies showed notable tumor size reduction. In conclusion, the PAL and TRA combination emerges as a promising strategy for overcoming PAL-induced resistance, offering a new horizon in breast cancer treatment.
- |||||||||| Mekinist (trametinib) / Novartis, BeiGene, Tafinlar (dabrafenib) / Novartis, BeiGene
Journal, IO biomarker: An overview of the contemporary diagnosis and management approaches for anaplastic thyroid carcinoma. (Pubmed Central) - Jul 1, 2024
Younger age, earlier tumor stage and radiotherapy are all prognostic factors for improved outcomes. Ultimately, therapeutic regimens should be tailored to the individual patient based on surveillance and epidemiological data, and a multidisciplinary approach is essential.
- |||||||||| Mekinist (trametinib) / Novartis, BeiGene, sirolimus / Generic mfg.
Journal: RAS isoform specific activities are disrupted by disease associated mutations during cell differentiation. (Pubmed Central) - Jun 27, 2024
In particular, the MEK-inhibitor trametinib could broadly restore differentiation, while the mTOR-inhibitor rapamycin broadly suppressed differentiation. We expect that this quantitative assessment of the impact of Ras-pathway mutants and drugs on cellular differentiation has great potential to complement cancer cell proliferation data.
- |||||||||| Mekinist (trametinib) / Novartis, BeiGene
Preclinical, Journal: Trametinib, a MEK1/2 Inhibitor, Protects Mice from Cisplatin- and Noise-Induced Hearing Loss. (Pubmed Central) - Jun 27, 2024
Trametinib also protected mice from noise-induced hearing loss and synaptic damage. This study shows that MEK1/2 inhibition protects against both insults of hearing loss, as well as that targeting all three kinases in the MAPK pathway protects mice from cisplatin- and noise-induced hearing loss.
- |||||||||| Mekinist (trametinib) / Novartis, BeiGene
Preclinical, Journal: Efficacy of Trametinib in Alleviating Cisplatin-Induced Acute Kidney Injury: Inhibition of Inflammation, Oxidative Stress, and Tubular Cell Death in a Mouse Model. (Pubmed Central) - Jun 27, 2024
Furthermore, trametinib significantly inhibited both apoptosis and necroptosis in the kidneys. In conclusion, our data underscore the potential of trametinib as a therapeutic agent for cisplatin-induced AKI, highlighting its role in reducing inflammation, oxidative stress, and tubular cell death.
- |||||||||| Mekinist (trametinib) / Novartis, BeiGene, Koselugo (selumetinib) / Merck (MSD), AstraZeneca
Review, Journal: Exploring New Drug Repurposing Opportunities for MEK Inhibitors in RASopathies: A Comprehensive Review of Safety, Efficacy, and Future Perspectives of Trametinib and Selumetinib. (Pubmed Central) - Jun 27, 2024
Moreover, there is evidence indicating that multiple pathways can contribute to these disorders, indicating a current need to more accurate understand of the underlying mechanism of the disease to apply an effective targeted therapy. In conclusion, while MEKi holds promise in managing life-threatening complications of RASopathies, dedicated clinical trials are required to establish standardized treatment protocols tailored to take into account the individual needs of each patient and favor a personalized treatment.
- |||||||||| Mekinist (trametinib) / Novartis, BeiGene, Keytruda (pembrolizumab) / Merck (MSD), Tafinlar (dabrafenib) / Novartis, BeiGene
P2 data, Journal, PD(L)-1 Biomarker, IO biomarker: Neoadjuvant pembrolizumab, dabrafenib and trametinib in BRAFV600-mutant resectable melanoma: the randomized phase 2 NeoTrio trial. (Pubmed Central) - Jun 22, 2024
P2
Pending longer follow-up, we suggest that immunotherapy and targeted therapy should not be combined in the neoadjuvant setting for melanoma. ClinicalTrials.gov registration: NCT02858921 .
- |||||||||| Mekinist (trametinib) / Novartis, BeiGene, Tafinlar (dabrafenib) / Novartis, BeiGene
Journal: Final Results for Adjuvant Dabrafenib plus Trametinib in Stage III Melanoma. (Pubmed Central) - Jun 20, 2024
P3
Among patients with melanoma with a BRAF V600E mutation, the results suggest that the risk of death was 25% lower with combination therapy. (Funded by GlaxoSmithKline and Novartis; COMBI-AD ClinicalTrials.gov number, NCT01682083; EudraCT number, 2012-001266-15.).
- |||||||||| Mekinist (trametinib) / Novartis, BeiGene, Cotellic (cobimetinib) / Exelixis, Roche
Journal: MEK Inhibitor-Associated Ocular Hypertension. (Pubmed Central) - Jun 17, 2024
All 3 patients' IOP returned to normal following dorzolamide/timolol administration and continued their cancer therapy...All 3 patients had a satisfactory response to topical pressure-lowering drops while continuing their life-preserving MEK inhibitor drug dose, indicating that discontinuation of therapy may not be necessary. Due to the increasing use of MEK inhibitors, it is important that ophthalmologists familiarize themselves with the broad range of potential adverse ocular effects of MEK inhibitors.
- |||||||||| Tevimbra (tislelizumab-jsgr) / BeiGene, Focus V (anlotinib) / Advenchen, Sino Biopharm
Biomarker, Clinical, Preclinical, Retrospective data, Review, Clinical Trial,Phase III, Journal, PD(L)-1 Biomarker: A patient with BRAF N581S mutation-positive lung adenocarcinoma demonstrates durable response to combined anlotinib and tislelizumab: A case report and literature review. (Pubmed Central) - Jun 15, 2024
Due to the increasing use of MEK inhibitors, it is important that ophthalmologists familiarize themselves with the broad range of potential adverse ocular effects of MEK inhibitors. We hope to bring more attention to rare non-V600 BRAF mutations by presenting this case of NSCLC.
- |||||||||| Tabrecta (capmatinib) / Incyte, Novartis, Mekinist (trametinib) / Novartis, BeiGene
Enrollment change, Trial completion date, Trial termination, Trial primary completion date, Metastases: Capmatinib Plus Trametinib for the Treatment of Metastatic Non-small Cell Lung Cancer With MET Exon 14 Skipping Mutation (clinicaltrials.gov) - Jun 10, 2024
P1, N=3, Terminated,
Seven of 10 patients completed the maximum 12 cycles of therapy or used trametinib as a bridge to HSCT and are alive with a median follow-up of 24 months. N=33 --> 3 | Trial completion date: Jun 2027 --> May 2024 | Recruiting --> Terminated | Trial primary completion date: Jun 2026 --> Nov 2023; slow accrual
- |||||||||| Journal: Resistance to anti-EGFR through the successive and cumulative acquisition of two new oncogenic addictions: BRAF and ALK (Pubmed Central) - Jun 10, 2024
Subsequent to additional progression and given the ALK rearrangement shown on the re-biopsy, 6th-line treatment with alectinib was proposed...This exceptional case is characterized by resistance to anti-EGFR through the successive and cumulative acquisition of two new oncogene addictions. The authors underline the importance of re-biopsy at each progression, leading (if at all feasible) to yet around round of targeted therapy.
- |||||||||| Mekinist (trametinib) / Novartis, BeiGene
Journal, Metastases: 4EBP1-mediated SLC7A11 protein synthesis restrains ferroptosis triggered by MEK inhibitors in advanced ovarian cancer. (Pubmed Central) - Jun 6, 2024
We further demonstrated that MEK inhibitor resistant OV cells were less vulnerable to trametinib-induced ferroptosis...Dual inhibition of MEK and mTOR/4EBP1 signaling restrained the protein synthesis of SLC7A11 via suppression of the mTOR-4EBP1 activity to reactivate ferroptosis in resistant cells. Together, these findings provide a promising therapeutic option for OV treatment through ferroptosis restoration by the combined inhibition of MEK and mTOR/4EBP1 pathways.
- |||||||||| DCC-3116 / Ono Pharma
Enrollment change, Trial completion date, Trial primary completion date, Combination therapy, Monotherapy, Metastases: A Phase 1/2 Study of DCC-3116 in Patients With RAS/MAPK Pathway Mutant Solid Tumors (clinicaltrials.gov) - May 31, 2024
P1/2, N=173, Recruiting,
Together, these findings provide a promising therapeutic option for OV treatment through ferroptosis restoration by the combined inhibition of MEK and mTOR/4EBP1 pathways. N=323 --> 173 | Trial completion date: Oct 2024 --> Aug 2028 | Trial primary completion date: Apr 2024 --> Aug 2027
- |||||||||| Mekinist (trametinib) / Novartis, BeiGene
Preclinical, Journal, PD(L)-1 Biomarker, IO biomarker: Inhibition of interferon regulatory factor 4 orchestrates T cell dysfunction, extending mouse cardiac allograft survival. (Pubmed Central) - May 30, 2024
In this study, we demonstrate that a novel ultra-low-dose combination of Trametinib and Rapamycin synergistically suppresses the MAPK and mTOR signaling network, leading to profound IRF4 inhibition, promoting allograft acceptance, and offering a potential new therapeutic strategy for improved transplant outcomes. However, further research is necessary to elucidate the underlying pharmacological mechanisms and facilitate translation to clinical practice.
- |||||||||| Stivarga (regorafenib) / Bayer
Journal, PD(L)-1 Biomarker, IO biomarker, Metastases: Regorafenib in patients with pretreated advanced melanoma: a single-center case series. (Pubmed Central) - May 27, 2024
REGO has a manageable safety profile in advanced melanoma patients, in monotherapy as well as combined with BRAF/MEK inhibitors or PD-1 blocking monoclonal antibodies. The triplet combination of REGO with BRAF/MEK inhibitors appears most active, particularly in the BRAF?V600mut patients.
- |||||||||| Mekinist (trametinib) / Novartis, BeiGene, Tafinlar (dabrafenib) / Novartis, BeiGene
Journal: Exploiting BRAF mutations in the therapeutic approach towards oral and maxillofacial tumors. (Pubmed Central) - May 26, 2024
A recent neoadjuvant therapy targeting BRAF, involving the use of dabrafenib and trametinib, has showcased a promising, safe, and effective strategy for organ preservation in the treatment of mandibular ameloblastoma. This convergence of molecular insights and targeted therapies holds the key to managing BRAF-mutated oral and maxillofacial tumors effectively, promising improved patient outcomes.
- |||||||||| Mekinist (trametinib) / Novartis, BeiGene, BI-3406 / Boehringer Ingelheim, buparlisib (AN2025) / Novartis, Adlai Nortye, Nippon Kayaku
Preclinical, Journal: Sex Matters-Insights from Testing Drug Efficacy in an Animal Model of Pancreatic Cancer. (Pubmed Central) - May 25, 2024
This combinatorial therapy reduced tumor weight more efficiently in male animals, although the drug concentrations were similar in the tumors of both sexes. These results underline the importance of sex-specific preclinical research and at the same time provide a solid basis for future studies with the tested compounds.
- |||||||||| Mekinist (trametinib) / Novartis, BeiGene, luminespib (AUY922) / Ligand
Journal: Zebrafish Avatars: Toward Functional Precision Medicine in Low-Grade Serous Ovarian Cancer. (Pubmed Central) - May 25, 2024
Tumor cells formed compact tumor masses (n = 84) in vivo, with clear Ki67 staining, indicating proliferation. Zebrafish xenografts exhibited sensitivity to trametinib and luminespib, individually or combined, within a two-week period, establishing them as a rapid and complementary tool to existing in vitro and in vivo models for evaluating targeted therapies in LGSOC.
- |||||||||| mirdametinib (PD-0325901) / SpringWorks Therap, BeiGene, Mekinist (trametinib) / Novartis, BeiGene, Koselugo (selumetinib) / Merck (MSD), AstraZeneca
Retrospective data, Journal: Incidence of Ophthalmological Complications in NF-1 Patients Treated with MEK Inhibitors. (Pubmed Central) - May 24, 2024
Some patients had pre-existing optic neuropathies (27%), but no instances of nerve changes occurred after commencing MEKi therapy. Four patients (15%) exhibited symptoms of dry eye, all of which were effectively managed with topical lubrication.
- |||||||||| Mekinist (trametinib) / Novartis, BeiGene, Zelboraf (vemurafenib) / Roche
Review, Journal: Advances in understanding and management of Erdheim-Chester disease. (Pubmed Central) - May 21, 2024
Definitive radiological results associated with ECD include hairy kidney, coated aorta, and cardiac pseudotumor. Treatment options primarily include anti-cytokine therapy and inhibitors of BRAF and MEK signaling.
- |||||||||| Journal, Metastases: Neoadjuvant Treatment of Locally Advanced Thyroid Cancer: A Preliminary Latin American Experience. (Pubmed Central) - May 17, 2024
We propose ALDH1A1 as a new potential target for treating melanoma resistant to MAPK/ERK inhibitors. While neoadjuvant therapy achieved tumoral responses, surgical resection was feasible in 50% of DTC, 33% of ATC, and 16% of MTC patients, with R0/R1 resection in 26% of the cohort, underscoring the need for patient selection and further research in this area.
- |||||||||| miransertib (MK-7075) / Merck (MSD), Ibrance (palbociclib) / Pfizer, Nerlynx (neratinib) / Puma
Journal, Combination therapy: Synergistic Effects of Neratinib in Combination With Palbociclib or Miransertib in Brain Cancer Cells. (Pubmed Central) - May 16, 2024
Notably, we found that treatment with neratinib in combination with palbociclib (CDK4/6 inhibitor), or miransertib (AKT1/2/3 inhibitor) resulted in synergistic growth inhibition of all HBCCLs. Our results support that repurposing drugs like neratinib in combination with the palbociclib or miransertib may be of therapeutic potential in brain cancer and warrants further investigations.
- |||||||||| Mekinist (trametinib) / Novartis, BeiGene
Journal, PD(L)-1 Biomarker, IO biomarker: D-mannose targets PD-1 to lysosomal degradation and enhances T cell-mediated anti-tumor immunity. (Pubmed Central) - May 15, 2024
Furthermore, D-mannose treatment dramatically improves the therapeutic efficacy of MEK inhibitor (MEKi) trametinib in vivo. Our findings unveil a universally unrecognized anti-tumor mechanism of D-mannose by destabilizing PD-1 and provide strategies to enhance the efficacy of both immune checkpoint blockade (ICB) and MEKi -based therapies.
- |||||||||| Mekinist (trametinib) / Novartis, BeiGene, Tagrisso (osimertinib) / AstraZeneca, Xpovio (selinexor) / Karyopharm, FORUS Therap
Biomarker, Journal, PD(L)-1 Biomarker, IO biomarker: HMGB1 Expression Levels Correlate with Response to Immunotherapy in Non-Small Cell Lung Cancer. (Pubmed Central) - May 14, 2024
Selinexor with a PD-1 inhibitor with or without trametinib abrogates the tumor growth in the murine Lewis lung cancer model. An in-depth exploration of the functions of HMGB1 mRNA and protein is expected to uncover new potential targets and provide a basis for treating metastatic NSCLC in combination with ICI.
- |||||||||| Braftovi (encorafenib) / Ono Pharma, Pierre Fabre, Pfizer, Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Pfizer
Trial completion, Trial completion date, Trial primary completion date, HEOR, Metastases: OCEANMIST: Comparative Effectiveness of Targeted Therapies in BRAF Positive Metastatic Melanoma in the US (clinicaltrials.gov) - May 13, 2024
P=N/A, N=1, Completed,
An in-depth exploration of the functions of HMGB1 mRNA and protein is expected to uncover new potential targets and provide a basis for treating metastatic NSCLC in combination with ICI. Active, not recruiting --> Completed | Trial completion date: Jul 2024 --> Dec 2023 | Trial primary completion date: Jul 2024 --> Dec 2023
- |||||||||| Review, Journal: RAF and MEK Inhibitors in Non-Small Cell Lung Cancer. (Pubmed Central) - May 11, 2024
New RAF and MEK inhibitors, with distinct biochemical characteristics, are in preclinical and clinical development. In this review, we aim to provide valuable insights into the current state of RAF and MEK inhibition in the management of NSCLC, fostering a deeper understanding of the potential impact on patient outcomes.
- |||||||||| Retrospective data, Journal, Real-world evidence, IO biomarker, Real-world effectiveness, Real-world, Metastases: Real-world efficacy and safety of BRAF-targeted therapy for patients with advanced melanoma: A single-center retrospective study in Japan. (Pubmed Central) - May 8, 2024
As a prognostic factor, performance status was associated with progression-free survival, and performance status, serum lactate dehydrogenase level, and dose interruption were associated with overall survival in the multivariate analysis. Real-world data on targeted therapy for patients with melanoma in Japan suggest that both dabrafenib?+?trametinib and encorafenib?+?binimetinib show similar efficacy and safety in Asian and White patients.
- |||||||||| Mekinist (trametinib) / Novartis, BeiGene, Tafinlar (dabrafenib) / Novartis, BeiGene
Retrospective data, Journal: Genetics-guided therapy in neuroendocrine carcinoma: response to BRAF- and MEK-inhibitors. (Pubmed Central) - May 8, 2024
BRAF-mutated NEC is sensitive to treatment with BRAF- and MEK-inhibitor combination. These results further support that DNA sequencing should be considered as standard of care in NECs to screen for potential treatment targets.
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