PDGFRA as a potential target in H3 K27M mutant gliomas

Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq

https://www.ncbi.nlm.nih.gov/pubmed/29674595

"We found that H3K27M-glioma primarily contain cells that resemble oligodendrocyte precursor cells (OPC-like), whereas more differentiated malignant cells are a minority. OPC-like cells exhibit greater proliferation and tumor-propagating potential than their more differentiated counterparts and are at least in part sustained by PDGFRA signaling."

PDGFRA is a receptor tyrosine kinase (like EGFR).  No PDGFRA inhibitors have been specifically approved for brain tumors, but inhibitors have been approved for other types of cancers.  Approved PDGFRA inhibiting drugs include imatinib, nilotinib, sorafenib, and dasatinib.

Agents for MGMT Unmethylated, PTEN Mutation, and PDGFRA Amplificayion

Hi,


My mother got the GBM surgery on Feb 6 this year. She is MGMT unmethylated, PTEN mutation, and PDGFRA amplification.


Does any one know effective agents for treating these disorders or symptoms?


Regards
James Zhou

Considering treatment options for high grade diffuse midline glioma H3k27m for my 8 year old daughter

Hi all,

Thanks so much to Stephen for your in depth reply to my questions about my 8 year old daughter and invitation to this blog. We moved to Norway in July and my daughter was diagnosed in early September with high grade diffuse midline glioma with H3K27m mutation after an extended biopsy, where it was determined that the tumor was not resectable. She underwent 3 further operations to have a double valve shunt put in to relieve hydrocephalus symptoms. She finished 6 weeks of radiation and Temodal about 10 days ago. The doctors want to start her on Temodal/Lomostine 4 weeks after radiation finished. If we follow this path, we could also have a full molecular analysis done and, upon recurrence, may possibly be able to access a trial using afatinib for BI1200.120, if applicable, or another targeted agent. I would also push for using repurposed drugs in the cocktail approach if possible and our conservative doctors could be convinced. 

We are trying to explore other options, and thanks to Stephen, learned about a new phase I peptide vaccine trial opening for paediatric glioma patients with mutation H3.3K27m based in San Fransisco. It is for patients who have completed 6 weeks of radiation and have not yet started chemo again, which is exactly where we are now. https://clinicaltrials.gov/ct2/show/NCT02960230

I am finding it so difficult to determine what would be the most promising, preferably least toxic option for my daughter. Any input on how promising a peptide vaccine targeted to this kind of mutation could be? Compared with temodar/lomostine/cocktail approach?

Many thanks in advance for your input.

Jeni