The role of FOXM1 and PD-L1 in malignant peripheral nerve sheath tumor resistance

A new mini review was published in Oncotarget's Volume 15 on September 30, 2024, entitled, "Linking FOXM1 and PD-L1 to CDK4/6-MEK targeted therapy resistance in malignant peripheral nerve sheath tumors."

As highlighted in the abstract of this paper, malignant peripheral nerve sheath tumors (MPNSTs) are aggressive, Ras-driven sarcomas characterized by the loss of the NF1 tumor suppressor gene and the hyperactivation of MEK and CDK4/6 kinases. Currently, MPNSTs lack effective therapies. Recently, the authors demonstrated the remarkable efficacy of dual CDK4/6-MEK inhibition in mice with de novo MPNSTs, which was further enhanced by targeting the immune checkpoint protein PD-L1. This triple combination therapy, targeting CDK4/6, MEK, and PD-L1, resulted in prolonged MPNST regression and improved survival, although most tumors eventually developed drug resistance. 

In their latest mini review, researchers Joshua J. Lingo, Ellen Voigt, and Dawn E. Quelle from the University of Iowa's Cancer Biology Graduate Program, Holden Comprehensive Cancer Center, Medical Scientist Training Program, Department of Neuroscience and Pharmacology, and Department of Pathology, explore the immune activation phenotype caused by CDK4/6-MEK inhibition in MPNSTs, emphasizing the unique involvement of intratumoral plasma cell accumulation. They also discuss how PD-L1 and FOXM1, a tumor-promoting transcription factor, are functionally linked and may serve as key mediators of resistance to CDK4/6-MEK targeted therapies. 

"We suggest that future therapeutic strategies targeting the oncogenic network of CDK4/6, MEK, PD-L1, and FOXM1 represent exciting future treatment options for MPNST patients."  

Source:
Journal reference:

Lingo, J. J., et al. (2024). Linking FOXM1 and PD-L1 to CDK4/6-MEK targeted therapy resistance in malignant peripheral nerve sheath tumors. Oncotarget. doi.org/10.18632/oncotarget.28650.

Comments

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
Post a new comment
Post

While we only use edited and approved content for Azthena answers, it may on occasions provide incorrect responses. Please confirm any data provided with the related suppliers or authors. We do not provide medical advice, if you search for medical information you must always consult a medical professional before acting on any information provided.

Your questions, but not your email details will be shared with OpenAI and retained for 30 days in accordance with their privacy principles.

Please do not ask questions that use sensitive or confidential information.

Read the full Terms & Conditions.

You might also like...
New tool predicts nerve damage risk from breast cancer treatment