Inhibiting kinases in malignant gliomas

Andrew, S.; Wen, Patrick Y.

doi:10.1517/14728222.11.4.473

Cited by 49 publications

(18 citation statements)

References 194 publications

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“…via the PAM pathway) is crucial in GBM and hence attractive for targeted therapy. [133,134] Unfortunately, the overall response rate of GBMs to kinase inhibitors in clinical trials has been poor so far. [135] One reason for these disappointing results may be inadequate trial design.…”

Section: Clinical Trials Of Kinase Inhibitors In Glioblastomamentioning

confidence: 99%

The role of the PI3K/AKT/mTOR pathway in brain tumor metastasis

Crespo¹,

Kind²,

Arcaro³

2016

JCMT

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The PI3K/AKT/mTOR (PAM) pathway is involved in a variety of cellular functions and often contributes to oncogenesis and cancer progression. It has been recognized that this pathway is frequently activated in the most common central nervous system cancers of adults and children, malignant gliomas and medulloblastomas (MB). In these tumors, the PAM network controls key functions necessary for cell invasion and metastasis, such as cell motility. This review summarizes the current knowledge about the role of PAM signaling in cell invasion and metastasis in gliomas and MB. Current approaches to inhibit cell invasion and metastasis by targeting the PAM pathway will also be discussed.

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Section: Clinical Trials Of Kinase Inhibitors In Glioblastomamentioning

confidence: 99%

The role of the PI3K/AKT/mTOR pathway in brain tumor metastasis

Crespo¹,

Kind²,

Arcaro³

2016

JCMT

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“…Strategies to determine the most promising combinations are important, as the number of potential therapeutic combinations is almost limitless [103] . There are several strategies that can be used to select targeted agents for combination therapy [104] . The target of first and second agents can be the same if they have different mechanisms of action and they together offer greater inhibition of target function.…”

Section: Combination Therapymentioning

confidence: 99%

Targeting multiple kinases in glioblastoma multiforme

Sathornsumetee

Reardon

2009

Expert Opinion on Investigational Drugs

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Glioblastoma multiforme (GBM), the most common primary malignant brain tumor in adults, is associated with high mortality. Current standard-of-care treatments, including surgery, radiation and chemotherapy, offer only palliation. Recent research in cancer therapy has shifted towards targeting the specific molecular aberrations that underlie the pathogenesis of cancers including GBM. Protein kinases are a family of enzymes that are key components in regulating cellular homeostasis. Protein kinases can be deregulated by several mechanisms, which contribute to cancer initiation and maintenance. Several protein kinases are important in gliomagenesis, thus representing new therapeutic targets in GBM. Low molecular weight inhibitors are the most commonly used agents to target protein kinases in the treatment of cancers. However, first-generation kinase inhibitors targeting only single kinases have demonstrated limited efficacy in unselected GBM patient populations. Several mechanisms of failure of monotherapy with single-targeted kinase inhibitors have been explained as new therapeutic strategies have emerged to overcome resistance. Simultaneous disruption of several kinases can be achieved by either multitargeted kinase inhibitors or combination of single-targeted kinase inhibitors with one another or with traditional cytotoxics. In this review, we will discuss the current clinical status of targeted therapy in GBM and recent approaches to target multiple kinases in this devastating cancer.

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“…These include the EGFR inhibitors gefitinib (Iressa, ZD1839; AstraZeneca, UK) and erlotinib (Tarceva, OSI-774; Genentech, CA, USA), the mTOR inhibitor temsirolimus (CCI-779; Wyeth, NJ, USA), and the farnesyltransferase inhibitor tipifarnib (R115777; Johnson & Johnson, NJ, USA) (Wen et al, 2006a;Chi and Wen, 2007). Inhibitors of signal transduction intermediates that indirectly inhibit angiogenesis have been generally well tolerated but have not demonstrated significant survival benefits as single agents in clinical trials.…”

Section: Other Angiogenic Growth Factor Pathwaysmentioning

confidence: 99%