ArticleClinical cancer research : an official journal of the American Association for Cancer Research2020
Phase I Trial of Trametinib with Neoadjuvant Chemoradiation in Patients with Locally Advanced Rectal Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 2 of them syntheses that pooled it.
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10 citing papers in PubMed, 2 syntheses or guidelines pooled it, 19 citations in OpenAlex.
- ESMO-ESTRO consensus statements on the safety of combining radiotherapy with EGFR, ALK, or BRAF/MEK inhibitors.ESMO open · 2026Pooled it
- 2021 American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer.Thyroid : official journal of the American Thyroid Association · 2021Guideline
- Combined MEK and PARP inhibition enhances radiation response in rectal cancer.Cell reports. Medicine · 2025Article
- Mitochondrial metabolic reprogramming in colorectal cancer: mechanisms of resistance and future clinical interventions.Cell death discovery · 2025Review
- Molecular mechanisms of tumor resistance to radiotherapy.Molecular cancer · 2023Review
- PTEN regulates invasiveness in pancreatic neuroendocrine tumors through DUSP19-mediated VEGFR3 dephosphorylation.Journal of biomedical science · 2022Article
- Article
- Oncogenic KRAS drives radioresistance through upregulation of NRF2-53BP1-mediated non-homologous end-joining repair.Nucleic acids research · 2021Article
- DNA damage repair: historical perspectives, mechanistic pathways and clinical translation for targeted cancer therapy.Signal transduction and targeted therapy · 2021Review
- Safety and Tolerability of Metastasis-Directed Radiation Therapy in the Era of Evolving Systemic, Immune, and Targeted Therapies.Advances in radiation oncologyReview
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Authors and funding
17 authors at 7 institutions in 1 country.
Funding
Abstract
purposeThe RAS/RAF/MEK/ERK signaling pathway is critical to the development of colorectal cancers, and PATIENTS AND
methodsPatients with stage II/III rectal cancer were enrolled on a phase I study with 3+3 study design, with an expansion cohort of 9 patients at the MTD. Following a 5-day trametinib lead-in, with pre- and posttreatment tumor biopsies, patients received trametinib and CRT, surgery, and adjuvant chemotherapy. Trametinib was given orally daily at 3 dose levels: 0.5 mg, 1 mg, and 2 mg. CRT consisted of infusional 5-FU 225 mg/m
resultsPatients were enrolled to all dose levels, and 18 patients were evaluable for toxicities and responses. Treatment was well tolerated, and there was one dose-limiting toxicity of diarrhea, which was attributed to CRT rather than trametinib. At the 2 mg dose level, 25% had pathologic complete response. IHC staining confirmed dose-dependent decrease in pERK with increasing trametinib doses.
conclusionsThe combination of trametinib with 5-FU CRT is safe and well tolerated, and may warrant additional study in a phase II trial, perhaps in a
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