- |||||||||| Journal, PD(L)-1 Biomarker, IO biomarker: Sarcoidosis-Like Reaction in Melanoma Patients Receiving Immunotherapy or Targeted Therapy. (Pubmed Central) - Dec 24, 2024
In all cases, the MDT played a crucial role in determining the course of treatment and balancing the risks of continuing or suspending cancer therapies while managing SLRs. National and international guidelines were consulted, but tailored decisions by the MDT were essential for optimizing patient care.
- |||||||||| Mekinist (trametinib) / Novartis, BeiGene, DT2216 / Dialectic Therap, Gilotrif (afatinib) / Boehringer Ingelheim
Journal: A novel regimen for pancreatic ductal adenocarcinoma targeting MEK, BCL-xL, and EGFR. (Pubmed Central) - Dec 18, 2024 along with a secondary pathway of P38 MAPK. Our study identifies an important contribution of EGFR inhibition to elevate the response of PDAC, supporting a clinical assessment of this triplet combination in patients.
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen, Mekinist (trametinib) / Novartis, BeiGene, Tafinlar (dabrafenib) / Novartis
Journal, IO biomarker: Adjuvant Radiation Therapy in Macroscopic Regional Nodal Melanoma. (Pubmed Central) - Dec 17, 2024 Generally, ART is now used at the first recurrence. The challenge now is to find which melanomas are truly radiosensitive if ART is to have any future role in this scenario.
- |||||||||| Mekinist (trametinib) / Novartis, BeiGene, Tafinlar (dabrafenib) / Novartis
Journal: Endocrine effects of MEK and BRAF inhibitor therapy in paediatric patients: a tertiary centre experience. (Pubmed Central) - Dec 13, 2024 The challenge now is to find which melanomas are truly radiosensitive if ART is to have any future role in this scenario. Clinicians using such treatments need to be aware of these potential effects, particularly the risk of hyponatraemia in patients with pre-existing central diabetes insipidus and monitor for these accordingly, including performing measurements of sodium and glucose prior to, during and after treatment.
- |||||||||| Preclinical, Journal: Combined MEK1/2 and ATR inhibition promotes myeloma cell death through a STAT3-dependent mechanism in (Pubmed Central) - Dec 12, 2024
Co-administration of the ATR inhibitor (ATRi) BAY1895344 (BAY) and MEK1/2 inhibitors, for example, cobimetinib, synergistically increased cell death in diverse MM cell lines...Similar events occurred in highly bortezomib-resistant (PS-R) cells, in the presence of patient-derived conditioned medium, and with alternative ATR (e.g. M1774) and MEK1/2 (trametinib) inhibitors...Finally, the ATR inhibitor/cobimetinib regimen significantly improved survival in MM xenografts, including bortezomib-resistant models, with minimal toxicity. Collectively, these findings suggest that combined ATR/MEK1/2 inhibition triggers dual STAT3 Tyr705 and Ser727 dephosphorylation, pronounced downregulation of cytoprotective targets and MM cell death, warranting attention as a novel therapeutic strategy in MM.
- |||||||||| Mekinist (trametinib) / Novartis, BeiGene
Journal: Enhancing efficacy of the MEK inhibitor trametinib with paclitaxel in KRAS-mutated colorectal cancer. (Pubmed Central) - Dec 12, 2024 Finally, the combination of trametinib with paclitaxel exhibited significant inhibition of tumor growth in several KRAS-mutant patient-derived xenograft mouse models. Our data provide evidence supporting clinical trials of trametinib with paclitaxel as a novel therapeutic option for patients with KRAS-mutated, metastatic CRC.
- |||||||||| Mekinist (trametinib) / Novartis, BeiGene, Koselugo (selumetinib) / Merck (MSD), AstraZeneca
Review, Journal: Reprogramming tumor-associated macrophages: The role of MEK-STAT3 inhibition in lung cancer. (Pubmed Central) - Dec 9, 2024 Preclinical studies have demonstrated the effectiveness of MEK inhibitors, such as trametinib and selumetinib, in synergistic therapies for NSCLC, particularly in modulating the tumor microenvironment. We analyse the present understanding of approaches that can transform TAMs via the inhibition of MEK-STAT3 with either solo or combined treatments in lung cancer therapy.
- |||||||||| Real World Outcomes in Adult Histiocytosis: 23-Year Canadian Single Center Analysis () - Dec 7, 2024 - Abstract #ASH2024ASH_7458;
Eight patients (72%) required subsequent therapies with cladribine in 4, vemurafenib in 2 and dabrafenib and trametinib combination in 2 patients...High incidence of second hematological malignancies in our small cohort warrants more efforts to establish the association between the two entities. Prospective, multicenter studies with molecular discoveries are needed in adult counterpart of this orphan disease.
- |||||||||| Mekinist (trametinib) / Novartis, BeiGene, Tafinlar (dabrafenib) / Novartis
Clinical, Retrospective data, Review, Journal: Dabrafenib plus trametinib in low-grade versus high-grade gliomas: a systematic review and meta-analysis. (Pubmed Central) - Nov 30, 2024 Dabrafenib plus trametinib is associated with favorable outcomes in gliomas, especially among those with lower age, BRAF V600 mutation, longer dual blockage treatment duration, and history of prior resection. The co-administration of dabrafenib and trametinib was associated with more favorable outcomes among LGGs than HGGs.
- |||||||||| Mekinist (trametinib) / Novartis, BeiGene, BMS-754807 / BMS
Journal: Ferroptosis-related prognostic model of mantle cell lymphoma. (Pubmed Central) - Nov 26, 2024 This study provides a prognostic model with ferroptosis-related gene signature for MCL. The results show that the model helps predict prognosis in MCL.
- |||||||||| Mekinist (trametinib) / Novartis, BeiGene
Journal: Trametinib alters contractility of paediatric Noonan syndrome-associated hypertrophic myocardial tissue slices. (Pubmed Central) - Nov 22, 2024 In summary, this study provides a comprehensive understanding of the interplay between M2 macrophages and cancer cells in glioma; utilizes a cross-talk gene signature to develop a predictive model that can predict the differentiation of patient prognosis, recurrence instances, and microenvironment characteristics; and aids in optimizing the application of trametinib in glioma patients. Ex vivo analysis of cultivated and electrically stimulated RV myocardial tissue slices of a patient with RAS-CM showed decreased contractility and improved sarcoplasmic reticulum function after addition of trametinib and in part after addition of rapamycin, but not after addition of dasatinib.
- |||||||||| carboplatin / Generic mfg.
Journal: Carboplatin desensitization in the era of target therapies: still worthwhile? (Pubmed Central) - Nov 20, 2024 Targeting the MEK/ERK pathway might help to develop new therapies or repurpose existing drugs for demyelinating diseases. Our study presented an interesting and cost-effective option where desensitization allowed children with HR to be treated with first-line therapy, avoiding the discontinuation of an effective treatment.
- |||||||||| Mekinist (trametinib) / Novartis, BeiGene, Tafinlar (dabrafenib) / Novartis
Journal: Axillary Lymph Node Malignant Melanoma of Unknown Primary Origin: A Case Report From Japan. (Pubmed Central) - Nov 18, 2024 Ten months after surgery, the patient experienced a favorable clinical course with no recurrence or complications from surgery or medication. The frequency and clinical characteristics of malignant melanoma differ among ethnic groups, and very few reports of MUP have been documented in East Asia.
- |||||||||| Cabometyx (cabozantinib tablet) / Exelixis
Enrollment open: Study of Targeted Therapy vs. Chemotherapy in Patients With Thyroid Cancer (clinicaltrials.gov) - Nov 18, 2024 P3, N=264, Recruiting, The frequency and clinical characteristics of malignant melanoma differ among ethnic groups, and very few reports of MUP have been documented in East Asia. Not yet recruiting --> Recruiting
- |||||||||| Jakafi (ruxolitinib) / Incyte, Mekinist (trametinib) / Novartis, BeiGene, SP600125 / BMS
Journal, Tumor cell: Prevention of liver metastasis via the pharmacological suppression of AMIGO2 expression in tumor cells. (Pubmed Central) - Nov 17, 2024 Using the MKN45 gastric cancer cells, we confirmed that ruxolitinib could prevent liver metastasis of human cancer cells. These results demonstrate that pharmacological inhibition of AMIGO2 expression in tumor cells is a promising novel strategy to prevent and control liver metastasis.
- |||||||||| Review, Journal, PD(L)-1 Biomarker: Histology Agnostic Drug Development: An Updated Review. (Pubmed Central) - Nov 15, 2024
We propose considerations for refining trial designs and emerging biomarkers, such as tumor neoantigen burden, to enhance patient selection. These findings illustrate the transformative potential of histology-agnostic therapies in precision oncology but highlight the need for continued research to optimize their use and overcome existing barriers.
- |||||||||| Mekinist (trametinib) / Novartis, BeiGene, navitoclax (ABT 263) / AbbVie, Tafinlar (dabrafenib) / Novartis
Trial completion date, Trial primary completion date, IO biomarker: NCI-2013-02103: Testing the Addition of Navitoclax to the Combination of Dabrafenib and Trametinib in People Who Have BRAF Mutant Melanoma (clinicaltrials.gov) - Nov 15, 2024 P1/2, N=75, Active, not recruiting, These findings illustrate the transformative potential of histology-agnostic therapies in precision oncology but highlight the need for continued research to optimize their use and overcome existing barriers. Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025
- |||||||||| Trial completion date, Trial termination, Trial primary completion date: A Study of Select Drug Combinations in Adult Patients With Advanced/Metastatic BRAF V600 Colorectal Cancer (clinicaltrials.gov) - Nov 14, 2024
P1, N=122, Terminated, Therefore, the findings of this computational study may be useful for early prognosis, diagnosis and therapies of NSCLC. Trial completion date: Jan 2025 --> Sep 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Jan 2025 --> Sep 2024; The decision of early termination was made due to business reasons, and was not based on any safety concerns for any of the treatment combinations.
- |||||||||| Mekinist (trametinib) / Novartis, BeiGene
Trial completion date: Trametinib in Treating Patients With Advanced Cancer With or Without Hepatic Dysfunction (clinicaltrials.gov) - Nov 13, 2024 P1, N=46, Active, not recruiting, Trial completion date: Jan 2025 --> Sep 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Jan 2025 --> Sep 2024; The decision of early termination was made due to business reasons, and was not based on any safety concerns for any of the treatment combinations. Trial completion date: Nov 2024 --> Nov 2025
- |||||||||| Review, Journal, PD(L)-1 Biomarker, IO biomarker: Targeted and cytotoxic inhibitors used in the treatment of lung cancers. (Pubmed Central) - Nov 13, 2024
On the order of 20?% of NSCLCs bear activating mutations in EGFR and are treated with osimertinib and other kinase antagonists...Local treatment options to control thoracic disease include radiotherapy and surgery. In patients with extensive-stage disease, a platinum agent (cisplatin or carboplatin) combined with etoposide and an anti-PDL1 inhibitor (atezolizumab or durvalumab) for four cycles followed by anti-PDL1 maintenance therapy is the recommended first-line regimen.
- |||||||||| Mekinist (trametinib) / Novartis, BeiGene, dactolisib (RTB101) / Adicet Bio
Journal: MEK inhibitor trametinib combined with PI3K/mTOR inhibitor BEZ-235 as an effective strategy against NSCLC through impairment of glucose metabolism. (Pubmed Central) - Nov 13, 2024 Furthermore, trametinib and BEZ-235 synergistically downregulated the expression of related proteins in the MAPK and PI3K/AKT/mTOR pathways, and decreased glucose consumption and lactic acid production through suppressing the expressions of glucose transporter 1 (GLUT1) and lactate dehydrogenase A (LDHA). These data imply that simultaneous inhibition of the MAPK and PI3K/AKT/mTOR pathways using trametinib combined with BEZ-235 could synergistically impair glucose metabolism, resulting in an obvious synergistic therapeutic effect against NSCLC.
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