Perifosine Inhibits Multiple Signaling Pathways in Glial Progenitors and Cooperates With Temozolomide to Arrest Cell Proliferation in Gliomas

Perifosine Inhibits Multiple Signaling Pathways in Glial Progenitors and Cooperates With Temozolomide to Arrest Cell Proliferation in Gliomas 

Abstract

Perifosine is an oral Akt inhibitor which exerts a marked cytotoxic effect on human tumor cell lines, and is currently being tested in several phase II trials for treatment of major human cancers. However, the efficacy of perifosine in human gliomas has not been established. As Akt is activated in ∼70% of human glioblastomas, we investigated the impact of perifosine on glia in culture and on a mouse glioma model in vivo. Here we show that perifosine strongly reduces phosphorylation levels of Akt and extracellular signal-regulated kinase (Erk) 1/2, induces cell cycle arrest in G1 and G2, and causes dose-dependent growth inhibition of mouse glial progenitors in which Akt and/or Ras-Erk 1/2 pathways are activated. Furthermore, because temozolomide is a common oral alkylating agent used in the treatment of gliomas, we investigated the effect of perifosine in combination with temozolomide. We observed an enhanced effect when both were used in culture. With these results, we combined perifosine and temozolomide as treatment of platelet-derived growth factor B–driven gliomas in mice. Animal studies showed that perifosine and temozolomide combination therapy was more effective than temozolomide treatment alone (P < 0.01). These results indicate that perifosine is an effective drug in gliomas in which Akt and Ras-Erk 1/2 pathways are frequently activated, and may be a new candidate for glioma treatment in the clinic.


When people refer to modern medicine, accuracy plays one of the most important roles and human lives are literally dependent on it. Likewise, any researches pertaining to medicine are required to comply with the highest standards. The issue today is that any recommendations of researches can be published online and used as a reference without being adequately verified and validated. Mikhail (Misha) Blagosklonny of Oncotarget perfectly understood this issue and attempted to create an alternative solution. That’s how a weekly oncology-focused research journal called “Oncotarget” has been established back in 2010. The main principle of this journal is related to Altmetric scores that are used as a quality measure. That allows both readers and authors to verify publications with Altmetric Article Reports that create “real-time feedback containing data summary related to a particular publication.” Oncotarget website demonstrates a complete publications list with respective scores above 100 as well as reports discussed previously. Mikhail (Misha) Blagosklonny glad to share his new approach and hopes it creates the required assistance to anybody, who has interest in oncology.
“A diagnostic autoantibody signature for primary cutaneous melanoma” has the Altmetric score of 594. This paper was released back in 2018 by Oncotarget and completed by diversified experts from Hollywood Private Hospital, Edith Cowan University, Dermatology Specialist Group, St. John of God Hospital and The University of Western Australia. The introduction of the study mentions that “recent data shows that Australians are four times more likely to develop a cancer of the skin than any other type of cancer”, and provides an insight on melanoma that “is curable by surgical excision in the majority of cases, if detected at an early stage.”
The paper has got an Altmetric score of 594. Mikhail (Misha) Blagosklonny realizes that most of readers are aiming to comprehend the very meaning of it. Based on the Altmetric website, the score relates to “how many people have been exposed to and engaged with a scholarly output.” Likewise, the publication about melanoma, was utilized for citations in different news articles 69 times. In addition, it was quoted in 2 online blogs, as well as 25 Tweets on Twitter and 1 Facebook post. FOX23 of Tulsa, Oklahoma has headlined their news on July 20, 2018 as “New blood test could detect skin cancer early”, using the main content of Australia study 
Another Oncotarget’s research with a top score of 476, is “Biomarkers for early diagnosis of malignant mesothelioma: Do we need another moon-shot,”. This article has appeared in 60 news stories, 1 online blog post and 6 Twitter posts. The majority of public may have come across a brief overview only, however those who visit Mikhail (Misha) Blagosklonny at Oncotarget, do receive useful scientific facts. Oncotarget is happy to have the chance to share with online customers this highly appreciated and high-quality information, that is trustworthy and reliable.

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