Ras pathway activation in gliomas: a strategic target for intranasal administration of perillyl alcohol.

Archivum Immunologiae Et Therapiae Experimentalis
Clóvis O Da FonsecaThereza Quirico-Santos

Abstract

Targeted therapy directed at specific molecular alterations is already creating a shift in the treatment of cancer patients. Malignant gliomas commonly overexpress the oncogenes EGFR and PDGFR and contain mutations and deletions of the tumor suppressor genes PTEN and TP53. Some of these alterations lead to activation of the P13K/Akt and Ras/MAPK pathways, which provide targets for therapy. Perillyl alcohol (POH), the isoprenoid of greatest clinical interest, was initially considered to inhibit farnesyl protein transferase. Follow-up studies revealed that POH suppresses the synthesis of small G proteins, including Ras. Intranasal delivery allows drugs that do not cross the blood-brain barrier to enter the central nervous system. Moreover, it eliminates the need for systemic delivery, thereby reducing unwanted systemic side effects. Applying this method, a phase I/II clinical trial of POH was performed in patients with relapsed malignant gliomas after standard treatment: surgery, radiotherapy, and chemotherapy. POH was administrated in a concentration of 0.3% volume/volume (55 mg) four times daily in an interrupted administration schedule. The objective was to evaluate toxicity and progression-free survival (PFS) after six months...Continue Reading

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Citations

Jun 26, 2010·Cancer Chemotherapy and Pharmacology·Sara J GreayManfred W Beilharz
Feb 11, 2014·Current Oncology Reports·Mohamed Ali Hamza, Mark Gilbert
Nov 22, 2013·Archivum Immunologiae Et Therapiae Experimentalis·Marcela D'Alincourt SalazarThereza Quirico-Santos
Apr 20, 2010·Journal of Cancer Research and Clinical Oncology·Clovis O da FonsecaThereza Quirico-Santos
Sep 8, 2009·Expert Opinion on Drug Delivery·Valentino LaquintanaGiuseppe Trapani
Dec 7, 2013·Biochemical and Biophysical Research Communications·Mitsuru ImamuraMakoto Dohi
Dec 9, 2014·Applied Biochemistry and Biotechnology·Shweta GuptaJohn R Porter
Dec 20, 2018·International Journal of Molecular Sciences·Thomas C ChenAxel H Schönthal
Aug 31, 2012·Molecular Cancer Therapeutics·Hee-Yeon ChoThomas C Chen
Mar 3, 2021·Antimicrobial Agents and Chemotherapy·Adriana A MarinLeonardo J M Carvalho

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Methods Mentioned

BETA
GTPases
lavage

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