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| http://dx.doi.org/10.3324/haematol.2017.174060 | DOI Listing |
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Hydroxychloroquine prevents resistance and potentiates the antitumor effect of SHP2 inhibition in NF1-associated malignant peripheral nerve sheath tumors.
Proc Natl Acad Sci U S A
January 2025
Cancer Biology & Genetics Program, Sloan Kettering Institute, New York, NY 10065.
Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas and the primary cause of mortality in patients with neurofibromatosis type 1 (NF1). These malignancies develop within preexisting benign lesions called plexiform neurofibromas (PNs). PNs are solely driven by biallelic loss eliciting RAS pathway activation, and they respond favorably to MEK inhibitor therapy.
View Article and Find Full Text PDFNeutrophilic Panniculitis Secondary to BRAF and MEK Inhibitor Therapy to Treat Stage IIIa Cutaneous Melanoma.
J Cutan Pathol
January 2025
Department of Dermatology, San Antonio Uniformed Services Health Consortium (SAUSHEC), San Antonio, Texas, USA.
Panniculitides are a group of inflammatory disorders of the subcutaneous fat that have been reported as a rare complication of both a serine threonine kinase BRAF inhibitor monotherapy and BRAF inhibition in combination with a mitogen activated protein kinase (MEK) inhibitor combination therapy used to treat metastatic melanoma. The cutaneous manifestations of BRAF and BRAF/MEK therapies have been well documented, but neutrophilic panniculitis remains a less common complication with fewer case reports. Physician awareness of this complication when following patients on similar targeted therapies can decrease delays in appropriate management.
View Article and Find Full Text PDFSynergistic two-step inhibition approach using a combination of trametinib and onvansertib in KRAS and TP53-mutated colorectal adenocarcinoma.
Biomed Pharmacother
January 2025
Department of Pharmacy, College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Gyeonggi-do 15588, Republic of Korea. Electronic address:
Colorectal malignancies associated with KRAS and TP53 mutations led us to investigate the effects of combination therapy targeting KRAS, MEK1, or PLK1 in colorectal cancer. MEK1 is downstream of RAS in the MAPK pathway, whereas PLK1 is a mitotic kinase of the cell cycle activated by MAPK and regulated by p53. Bioinformatics analysis revealed that patients with colorectal cancer had a high expression of MAP2K1 and PLK1.
View Article and Find Full Text PDFEnhancing efficacy of the MEK inhibitor trametinib with paclitaxel in -mutated colorectal cancer.
Ther Adv Med Oncol
December 2024
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
Background: is frequently mutated in the tumors of patients with metastatic colorectal cancer (mCRC) and thus represents a valid target for therapy. However, the strategies of targeting KRAS directly and targeting the downstream effector mitogen-activated protein kinase kinase (MEK) via monotherapies have shown limited efficacy. Thus, there is a strong need for novel, effective combination therapies to improve MEK-inhibitor efficacy in patients with -mutated mCRC.
View Article and Find Full Text PDFPhase II study of MEK inhibitor trametinib alone and in combination with AKT inhibitor GSK2141795/uprosertib in patients with metastatic triple negative breast cancer.
Breast Cancer Res Treat
December 2024
Division of Medical Oncology, Ohio State University College of Medicine, Columbus, OH, USA.
Purpose: While MEK inhibitors demonstrated activity in metastatic triple negative breast cancer (mTNBC) preclinical studies, preclinical, and clinical studies implicate rapid development of resistance limiting clinical benefit. The purpose of this study was to determine response rate for Trametinib alone and in combination with Uprosertib in patients with mTNBC previously treated with chemotherapy.
Methods: This was an open-label, two-part, phase II, single-arm, multicenter study.
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