December research from Priscilla and her lab at MGH into breast...

December research from Priscilla and her lab at MGH into breast brain cancer.

Her work and information released, regarding BCBM is absolutely critical here - prior to likely data releases in two KZA Clinical Trials in April at AACR.

Deep exhaustive studies which this time, focuses on PI3K pathway activation through hypoxic signaling.
(Investors understand by now, the KZA drug Paxalisib inhibits (repairs) these aberrations in the PI3K/AKT/mTOR pathway in genomic cancer driver abnormalities. )


From this research :

"The selective activation of hypoxic signaling by metastatic breast cancer in the brain may have therapeutic implication"

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PI3K/Akt and HIF‑1 signaling pathway in hypoxia‑ischemia ...

https://pubmed.ncbi.nlm.nih.gov/30106145
Previous studies have demonstrated that the phosphatidylinositol‑3 kinase (PI3K)/protein kinase B (Akt) signaling pathway, which regulates a wide range of cellular functions, is involved in the resistance response to H‑I through the activation of proteins associated with survival and inactivation of apoptosis‑associated proteins.


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HIF1A signaling selectively supports proliferation of breast cancer in the brain

• December 2020
• Nature Communications 11(1)

DOI: 10.1038/s41467-020-20144-w


David T. Ting


Priscilla K. Brastianos



Blood-borne metastasis to the brain is a major complication of breast cancer, but cellular pathways that enable cancer cells to selectively grow in the brain microenvironment are poorly understood. We find that cultured circulating tumor cells (CTCs), derived from blood samples of women with advanced breast cancer and directly inoculated into the mouse frontal lobe, exhibit striking differences in proliferative potential in the brain. Derivative cell lines generated by serial intracranial injections acquire selectively increased proliferative competency in the brain, with reduced orthotopic tumor growth. Increased Hypoxia Inducible Factor 1A (HIF1A)-associated signaling correlates with enhanced proliferation in the brain, and shRNA-mediated suppression of HIF1A or drug inhibition of HIF-associated lycolytic pathways selectively impairs brain tumor growth while minimally impacting mammary tumor growth. In clinical specimens, brain metastases have elevated HIF1A protein expression,compared with matched primary breast tumors, and in patients with brain metastases, hypoxic signaling within CTCs predicts decreased overall survival. The selective activation of hypoxic signaling by metastatic breast cancer in the brain may have therapeutic implication