TED Talks - William Li: Can we eat to starve cancer?
Very interesting
As per the cancer Torch's wife has, I found this:
Therapeutic Advances in the Treatment of Glioblastoma: Rationale and Potential Role of Targeted Agents
Abstract
Despite advances in standard therapy, including surgical resection followed by radiation and chemotherapy, the prognosis for patients with glioblastoma multiforme (GBM) remains poor. Unfortunately, most patients die within 2 years of diagnosis of their disease. Molecular abnormalities vary among individual patients and also within each tumor. Indeed, one of the distinguishing features of GBM is its marked genetic heterogeneity. Nonetheless, recent developments in the field of tumor biology have elucidated signaling pathways and genes involved in the development of GBM, and several novel agents that target these signaling pathways are being developed. As new details on the genetic characteristics of this disease become available, innovative treatment regimens, including a variety of traditional treatment modalities such as surgery, radiation, and cytotoxic chemotherapy, will be combined with newer targeted therapies. This review introduces these new targeted therapies in the context of current treatment options for patients with GBM. It is hoped that this combined approach will overcome the current limitations in the treatment of patients with GBM and result in a better prognosis for these patients.
[snip]
Angiogenesis Inhibitors
The growth and survival of GBM are dependent on an adequate blood supply, and not surprisingly, malignant gliomas are highly vascularized [10]. The formation of new blood vessels is coordinated by the complex interaction of many angiogenic factors, including VEGF, basic fibroblast growth factor (bFGF), and PDGF [10]. Therefore, targeting factors and pathways implicated in angiogenesis may represent potential approaches to the treatment of this disease.
Because VEGF represents a major stimulatory factor for the initiation of angiogenesis, the inhibition of VEGFRs is a promising treatment for malignant gliomas [10, 20]. PTK787/ZK 222584 (Novartis Pharmaceuticals Corporation and Schering AG Corporation), a VEGFR tyrosine kinase inhibitor, decreases glioma growth and vascularization in vivo and is currently being investigated in phase I/II trials alone or in combination with lomustine or temozolomide in patients with GBM [10, 35].
Other VEGFR inhibitors, including ZD6474 (Zactima™; AstraZeneca Pharmaceuticals) and CEP-7055 (sanofi-aventis, Bridgewater, NJ), have produced significant growth inhibition of glioblastoma xenografts in nude mice [10]. Clinical trials of these and other VEGFR inhibitors, such as sorafenib (BAY 43-9006; Bayer Pharmaceuticals Corporation, West Haven, CT, and Onyx Pharmaceuticals, Emeryville, CA) and AZD2171 (AstraZeneca Pharmaceuticals), are ongoing or being planned [10, 36].
In recent trials, monotherapy with thalidomide (Thalomid®; Celgene Corporation, Warren, NJ) has been investigated for the treatment of GBM because of its antiangiogenic effects. However, results suggest thalidomide alone has only moderate antitumor activity in patients with recurrent high-grade gliomas [20, 37]. Nonetheless, the combination of thalidomide and chemotherapy appears to be more active in patients with recurrent gliomas than either agent alone [20, 38]. The αvβ3 integrin inhibitor cilengitide (EMD 121974; EMD Pharmaceuticals, Durham, NC) induces apoptosis in brain tumor cells, and the protein kinase C (PKC) β2 inhibitor enzastaurin (LY317615; Eli Lilly and Company, Indianapolis) decreases VEGF levels in a mouse tumor model [39, 40]. Phase II trials in recurrent gliomas are under way for both of these agents [10]. Furthermore, metalloproteinase inhibitors, including SI-27 (Shionogi and Company Ltd., Osaka, Japan) and batimastat (British Biotech Pharmaceuticals, Ltd., Oxford, UK), inhibit angiogenesis invasion in vivo and have therapeutic potential for the treatment of GBM [10, 41]. Other angiogenic inhibitors of interest include cyclooxygenase 2 (COX-2) inhibitors, angiostatin, atrasentan (Abbott Laboratories, Abbott Park, IL), and lenalidomide (Revlimid®; Celgene Corporation) [10, 20, 42–44].
A new approach for delivering antiangiogenic agents to gliomas uses naked plasmid DNA targeted to brain tumors via intra-arterial injection [45]. The intra-arterial delivery of the gene for endostatin, a suppressor of angiogenesis, was recently investigated in a rat gliosarcoma model. Administration of the endostatin gene resulted in an 80% tumor volume reduction, and survival time was up to 47% longer [45].
To achieve the greatest therapeutic benefit from antiangiogenic agents, it will be important to determine the most effective combinations of therapies and drugs. Agents that target multiple receptors, including sorafenib, valatinib (PTK787/ZK222584), sunitinib (SU011248) (Pfizer Pharmaceuticals, New York), ZD6474 (zactima) and AEE788, allow a multipronged attack against vascularization (Table 1⇑) [10, 46]. Ultimately, the most effective treatment strategies may be tailored to the molecular phenotype of a patient’s tumor and include chemotherapy in combination with cytostatic agents.
Bevacizumab (Avastin®; Genentech, Inc., South San Francisco, CA), a recombinant, humanized monoclonal antibody targeting VEGF, has been recently approved for use in colorectal carcinoma based on a significant survival benefit observed following its addition to fluorouracil-based chemotherapy [47]. Similarly, Stark-Vance recently reported that, among 21 patients with recurrent malignant glioma treated with bevacizumab plus irinotecan (Camptosar®; Pfizer Pharmaceuticals), one patient achieved a complete response, eight achieved partial responses, and 11 achieved stable disease [48]. Overall, the regimen was reported as well tolerated, although two deaths occurred on treatment, including one patient with an intracranial hemorrhage and one patient with bowel perforation. A formal, single-arm phase II study of bevacizumab plus irinotecan is being performed at the Preston Robert Tisch Brain Tumor Center at Duke University Medical Center for patients with recurrent malignant glioma. Preliminary analyses of results of this trial reveal that this regimen is well tolerated among malignant glioma patients and is associated with a highly exciting rate of radiographic response. Further investigation of the regimen of bevacizumab plus irinotecan is planned.