The latest, hand-selected news for glioblastoma patients
- Two researchers from MD Anderson Cancer Center discuss the latest, encouraging advances in molecular targeting of gliomas.
Curr Opin Neurol. 2007 Dec;20(6):712-8.
PubMed ID: 17992095
- Initial results of a thalidomide analogue called lenalidomide. Like thalidomide, lenalidomide is an angiogenesis inhibitor and did not show significant activity as a monotherapy in gliomas, but it may hold promise as part of a multi-therapy.
Clin Cancer Res. 2007 Dec 1;13(23):7101-6.
PubMed ID: 18056189
- Scripps researchers demonstrate that neutrophils, the most common type of white blood cell, actually help tumors grow by responding to inflammation and releasing protease matrix metalloproteinases type 9, or proMMP-9, which then promotes angiogenesis.
- Celldex Therapeutics announces that their EGFRvIII vaccine for GBM has just received orphan drug status.
- A report from New York University on bevacizumab (Avastin) in high grade gliomas, reporting results as good as recent Duke studies: in recurrent disease a PFS-6 of 71%. This article also includes a call to make Avastin a frontline treatment for high-grade gliomas.
- Japanese researchers report on a Phase I study which demonstrates that the combination of temozolomide and VP-16 is well-tolerated and shows activity in recurrent gliomas.
Surg Neurol. 2008 Jan;69(1):46-50.
PubMed ID: 18054615
- An MD Anderson case study using temozolomide with immunotherapy treatments demonstrating that these two potentially conflicting treatments can be given successfully, and perhaps even synergistically.
Neuro Oncol. 2007 Dec 13.
PubMed ID: 18079360
- UCLA researchers demonstrate that using adenoviruses expressing Flt3L (human soluble FMS-like tyrosine kinase 3 ligand) and TK (herpes simplex virus type 1-thymidine kinase) in an animal model with implanted GBM results in long-term survivors in 50-70% of the animals.
Neuro Oncol. 2007 Dec 13.
PubMed ID: 18079358
- UK researchers find that caffeine, which inhibits G2/S phase checkpoint activation, can radiosensitize many human glioma cell lines.
Neuro Oncol. 2007 Oct;9(4):404-11.
PubMed ID: 17704360
- Another remarkable herbal extract from China called gambogic acid, from the resin of the Garcinia hanburryi tree of SE Asia, which appears to have therapeutic value against glioblastoma both in vitro and in vivo.
Biochem Pharmacol. 2007 Nov 9.
PubMed ID: 18070617
- Compelling evidence that a monoclonal antibody called alphaPlGF may be effective against placental growth factor (PlGF), a VEGF homolog, and not only inhibits tumor angiogenesis but does so without adversely affect healthy tissues.
Cell. 2007 Nov 2;131(3):463-75.
PubMed ID: 17981115
- TransMolecular, Inc. reports initial data for experimental use in 5 glioma patients of a radiolabeled version of its synthetic scorpion venom peptide, TM-601. This study proved that the synthetic chlorotoxin can cross the blood brain barrier, bind to glioma cells, and result in radiographic improvement.
- British study finds that the addition of carmustine wafers (Gliadel) during surgery does not confer a significant survival advantage grade III and IV patients, adding a median of 2.3 months.
- More good news about using Avastin, both as monotherapy and adjuvant treatment, in a large UCLA study presented at the 12th Annual SNO meeting.
- Updated temozolomide treatment statistics from a large, followup study of 573 patients.
- Updated data from the Mayo Clinic on the EGFRviii-specific immunotherapy treatment from Celldex Therapeutics called CDX-110.
- Abstracts for the Twelfth Annual Meeting of the Society for Neuro-Oncology (SNO), November 15-18, 2007.
Click for PDF Download...
- Intriguing research indicates that someday soon people may be able to diagnose glioblastomas well before they mature using a simple blood test.
- The Regensburg, Germany-based company is using a cash investment to fund a Phase III trial of its lead drug candidate, AP 12009, an antisense translational inhibitor of transforming growth factor-beta2 (TGF-beta2), which is in development for treating malignant gliomas. The study is due to begin next year in centers in Europe, North America and Asia.
- Northwest Biotherapeutics announces that the first patients have been enrolled in its US Phase II immunotherapy trial for DCVax-Brain. The company expects to enroll 141 patients from 10 clinics, with completion of patient accrual by the end of 2007.
- Interesting evidence that specific immune factors related to the prevalence of allergies, especially IL-4, may affect glioblastoma development.
- A large meta-analysis study from Harvard, also showing a "strong inverse relationship" between atopic disease and gliomas.
J Natl Cancer Inst. 2007 Oct 17;99(20):1544-50. Epub 2007 Oct 9.
PubMed ID: 17925535
A lay review of this study...
- A updated overview of glioblastoma molecular biology.
Neurocirugia (Astur). 2007 Oct;18(5):373-82.
PubMed ID: 18008011
- A retrospective study of 245 British glioma patients demonstrates that patients with grade III tumors which appear radiologically as glioblastoma should be managed as glioblastoma.
Radiother Oncol. 2007 Nov 20 [Epub ahead of print].
PubMed ID: 18035440
- A remarkable case report of a GBM patient's tumor disappearing after experimental photodynamic therapy.
J Neurooncol. 2007 Nov 23 [Epub ahead of print].
PubMed ID: 18034212
- More evidence that the presence of glutamine plays an important role in the proliferation of glioblastoma cells.
Proc Natl Acad Sci U S A. 2007 Nov 21 [Epub ahead of print].
PubMed ID: 18032601
- A summary of promising new therapies for gliomas from well-known neuro oncologist Dr. Howard Fine, chief of the Neuro-Oncology Branch at NCI's Center for Cancer Research. Perhaps most importantly, Dr. Fine here endorses molecular profiling of individual tumors to identify biomarkers for more individualized treatments.
Cancer J. 2007 Nov-Dec;13(6):349-54.
PubMed ID: 18032970
- Another in vitro study showing that inhibition of telomerase in glioblastoma cells disrupts tumor angiogenesis, and in fact, telomerase upregulation by endothelial cells is required for GBM tumor angiogenesis.
Int J Cancer. 2007 Nov 20 [Epub ahead of print].
PubMed ID: 18027853
- An in vitro study of the old hypomethylating drug 5AzadC which changes the expression of key genes in the tumorigenesis process. 5azadC downregulated hTERT and telomerase expression in glioma cell lines, suggesting that 5azadC may be an appropriate therapeutic drug in combination with non-alkylating agents, such as cisplatin, taxol, and tamoxifen.
Brain Res. 2007 Oct 26 [Epub ahead of print].
PubMed ID: 18021753
- A compelling study supporting a novel chemoimmunotherapy regimen using all-trans retinoic acid and interferon-gamma.
Neurochem Res. 2007 Dec;32(12):2203-9. Epub 2007 Aug 4.
PubMed ID: 17676389
- An in vitro study of curcumin against the U87MG cell line by Medical University of South Carolina, showing dose-dependent suppression of anti-apoptotic factors and activation of calpain and caspase proteolytic cascades for apoptosis.
Neurochem Res. 2007 Dec;32(12):2103-13. Epub 2007 Jun 12.
PubMed ID: 17562168
- A Japanese in vitro study showing that inhibition of thrombin, a coagulation protein, reduced expression of platelet derived growth factor-B, and thus cell proliferation, in glioblastoma cells in vitro. The same team earlier found that thrombin could be inhibited by hirudin, an anticoagulant occurring naturally in medicinal leeches.
J Thromb Haemost. 2007 Nov;5(11):2219-26.
PubMed ID: 17958740
- An interesting study on the over-expression of heat shock proteins in brain tumor cell lines.
J Neurosci. 2007 Oct 17;27(42):11214-27.
PubMed ID: 17942716
- Guidelines for getting optimal analysis when using immunohistochemical assessments of MGMT expression.
Acta Neuropathol. 2007 Oct 27 [Epub ahead of print].
PubMed ID: 17965865
- An excellent pharmacological investigation into the anti-inflammatory and anti-tumor mechanisms of berberine, an herbal alkaloid found in several plants, which suppresses NF-kappaB and Akt activation.
Eur J Pharmacol. 2008 Feb 2;580(1-2):70-9.
PubMed ID: 18083161
- Results from a large, international trial demonstrate that radiation therapy with adjuvant temozolomide results in quadruple the number of long-term survivors.
- Researchers at Duke find that 90% of glioblastoma patients are infected with a particular virus, the human cytomegalovirus (HCMV).
- New trial of the immunotherapy treatment CDX-110 from Celldex Therapeutics opens enrollment in over 20 cancer centers across the U.S. after promising results in small-scale trials.
- AngioChem announces FDA approval for a glioblastoma Phase I/II trial of ANG1005, a conjugated molecule which transports chemo drugs like paclitaxel across the blood brain barrier.
- Biomira presents preclinical data for it's small molecule drug PX-866 which inhibits phosphatidylinositol-3-kinase (PI-3 kinase) in glioblastoma.
- Tapestry Pharmaceuticals presents preclinical data for its taxane derivative, TPI 287, which has shown in vitro activity in chemo-resistant tumor types, including glioblastoma.
- Bradmer Pharmaceuticals announces FDA approval for a Phase III trial of Neuradiab, a small molecule inhibitor developed at Duke University which blocks tenascin-C, which is overexpressed in glioblastoma.
More Info on the Phase I and II trials...
- Patient accrual in UCSF's Phase II Oncophage immunotherapy trial has begun, one of the few immunotherapies available for recurrent glioma patients.
- University of Pennsylvania researchers find that the brain-specific gene BAI1 (brain-specific angiogenesis inhibitor 1) is missing in most glioma and glioblastoma cell lines, and probably helps these cells avoid normal apoptosis.
More about BAI1...
- Results from a Duke study showing promising results in recurrent glioblastoma using Avastin and CPT-11. PFS-6 was 46%, 6-month overall survival was 77%, and under 12% had blood clots.
J Clin Oncol. 2007 Oct 20;25(30):4722-9.
PubMed ID: 17947719
- Chinese researchers report synergy in killing glioblastoma cell lines in vitro using Lovastatin, the cholesterol-lowering drug found naturally in red yeast rice, and hTRAIL.
J Neurooncol. 2007 Oct 11.
PubMed ID: 17928957
- Confirmation that the promising serine protease inhibitor called pigment epithelium-derived factor (PEDF) is a potent, but expensive, inhibitor of glioma malignancies, as it is against many other types of cancer.
Life Sci. 2007 Sep 29;81(16):1256-63. Epub 2007 Sep 1.
PubMed ID: 17919663
More Background Info on PEDF...
- An Israeli in vitro study showing that temozolomide's effectiveness is dose-dependent and may upregulate HIF and VEGF, suggesting that standard treatment might benefit from inhibiting these proteins.
Cancer J. 2007 September/October;13(5):335-344.
PubMed ID: 17921733
- An Israeli study to isolate anti-inflammatory agents from boswellia identifies incensole acetate, which inhibits nuclear factor (NF)-kappa B.
Mol Pharmacol. 2007 Sep 26.
PubMed ID: 17921733
- A report from USC about the green tea polyphenol EGCG and how it can sensitize malignant glioma cells to temozolomide, which is good. Note, however, that EGCG can also demethylate MGMT, which is bad when using temozolomide.
Cancer Res. 2007 Oct 15;67(20):9809-9816.
PubMed ID: 17942911
- An MD Anderson study showing that a new, small molecule STAT3 inhibitor can significantly overcome the immunosuppression found in glioblastoma cell lines, in vitro.
Cancer Res. 2007 Oct 15;67(20):9630-6.
PubMed ID: 17942891
- Korean researchers describe the successful induction of apoptosis in glioma cell lines using ciglitazone, a synthetic PPARgamma agonist. Interestingly, it's mode of action was blocked by the antioxidant N-acetylcysteine (NAC).
Neurochem Res. 2007 Oct 17.
PubMed ID: 17940898
- Another in vitro study showing that delta(9)-THC, the constituent extract of cannabis (marijuana), significantly affects the viability of GBM cell lines. In another study, the Max-Planck-Institute has shown just the opposite.
Acta Oncol. 2007 Oct 12;:1-9.
PubMed ID: 17934890
Compare this study to PubMed ID: 15026328
- A Spanish study which concludes that "melatonin's oncostatic effect on glioma cells is mediated, at least in part, by the inhibition of protein kinase C activity which, in turn, results in Akt and NF-kappaB activity inhibition and modulation of cell cycle-related gene expression."
J Pineal Res. 2007 Oct;43(3):239-44.
PubMed ID: 17803520
- A review of the current state of glioma treatments, with special emphasis on molecular targets.
- A preclinical study from Dana-Farber demonstrating that a multitreatment of Gleevec, Tarceva, and the Met kinase inhibitor SU11274 is highly effective at killing glioblastoma cells in vitro.
Even More Info...
- The much-anticipated human trial of the substance DCA begins at Univ. of Alberta.
Update letter from Dr. Michelakis, MD
- Research at Stanford has created a "molecular probe" which causes glioma cells to light up via a fluorescent protease, allowing surgeons to differentiate normal tissue and malignancies.
- Chinese researchers report that the traditional Chinese herb lei gong teng (Tripterygium wilfordii) induced dose-dependent apoptosis in U87MG and U251MG cell lines via a p53-independent pathway.
J Int Med Res. 2007 Jul-Aug;35(4):490-6.
PubMed ID: 17697526
- Researchers at Medical University of South Carolina find that the garlic compounds DAS, DADS, and DATS are cytotoxic to the T98G and U87MG cell lines in a dose-dependent manner.
Cancer. 2007 Sep 1;110(5):1083-95.
PubMed ID: 17647244
- A review of common characteristics found amongst long-term GBM survivors in Germany. Nothing surprising or new appears to have been found.
Brain. 2007 Oct;130(Pt 10):2596-606. Epub 2007 Sep 4.
PubMed ID: 17785346
- Italian researchers have assessed the immunotherpeutic value of a variety of interleukins (proteins which stimulate the immune system) and have discovered that IL-21 shows great promise in gliomas.
Int J Cancer. 2007 Oct 15;121(8):1756-63.
PubMed ID: 17582604
- A very interesting study from Johns Hopkins reporting that Vitamin C and N-acetylcysteine (NAC) are not only antioxidants, but also hypoxia-inducible factor (HIF)-1 inhibitors.
Cancer Cell. 2007 Sep;12(3):230-8.
PubMed ID: 17785204
- A study which demonstrates melatonin inhibiting C6 glioma cells in vitro via aromatase inhibition, which effects estrogen production. Curiously, many other studies show that gliomas express little or no estrogen receptors, so while the study supports the use of melatonin, their interpretation of the mechanism may be controversial.
Br J Cancer. 2007 Sep 17;97(6):755-60.
PubMed ID: 17700567
- An updated version of Ben Williams' invaluable treatment overview.
- Long-developed EGFR inhibitor nimotuzumab (earlier called h-R3),which may not cause severe acne rashes like Tarceva, begins new, multi-center glioblastoma trial in Europe.
- A study reporting that a 1 week on/1 week off temozolomide schedule is less toxic than a low-dose schedule while still depleting MGMT.
- Clarifications from Northwest Biotherapeutics regarding their July announcement of Swiss approval of their DCVax-Brain immunotherapy treatment.
- More evidence from Johns Hopkins research that cyclopamine-mediated hedgehog pathway inhibition may be an important treatment strategy in glioblastomas.
Stem Cells. 2007 Jul 19.
PubMed ID: 17628016
- An overview concerning the relationship between nitric oxide and VEGF, and how dietary components may be able to influence angiogenesis via this relationship.
Curr Cancer Drug Targets. 2007 Aug;7(5):475-83.
PubMed ID: 17691907
- An essay on WebMD.com discussing potential harmful impacts of VEGF inhibitors, such as Avastin.
- The Swiss have approved the first brain tumor vaccine for the general patient population, the DCVax-Brain dendritic cell immunotherapy treatment from Seattle-based Northwest Biotherapeutics.
- Development of new cytotoxins effective in glioblastoma, based on analogues of norcantharidin, an insect toxin which inhibits protein phosphatase type 2A, possibly without any hemopoietic (blood-related) side effects.
Bioorganic & Medicinal Chemistry. 2007 Jun 20; [Epub ahead of print].
PubMed ID: 17606377
- A new clinical trial begins for the conjugated molecule study drug Cotara, from Peregrine Pharmaceuticals. Cotara, which is delivered via CED, selectively irradiates necrosis and has shown moderate efficacy in heavily pre-treated patients.
- An overview of the state of small molecule, targeted therapies in brain tumors, including EGFR, mTOR, PKC and VEGFR inhibitors.
Molecular Cancer Therapeutics 6, 1909-1919, July 1, 2007.
PubMed ID: (Unknown yet)
- Promising results from a Japanese feasability study of a new GBM vaccine tested in largely pre-treated patients, called autologous formalin-fixed tumor vaccine (AFTV).
Cancer Science. 2007 Aug;98(8):1226-33 (Epub 2007 May 22).
PubMed ID: 17517052
- A report from UCSF that I-125 brachytherapy followed by RT results in "high toxicity and reoperation rates, without demonstrated improvement in survival."
International journal of radiation oncology, biology, physics. 2007 May 16
PubMed ID: 17512132
- An excellent summary at VirtualTrials.com of all brain tumor extracts presented at ASCO 2007. Thanks, Al!
- An update on the drug AP 12009, a TGF-beta 2-inhibitor, from Antisense Pharma at ASCO 2007. As a monotherapy, AP 12009 produced results as good as temozolomide.
- More fantastic results presented at ASCO 2007 for the EGFRvIII Vaccine (CDX-110) from Celldex Therapeutics. Median survival times are almost 2.5 years and preliminary findings suggest that the vaccine can be used concomitant with temozolomide.
- More data presented at ASCO 2007 for the pan-VEGF inhibitor AZD2171 (Recentin or cediranib), based on a small study of 31 recurrent glioblastoma patients who had failed prior therapies. Survival rates for AZD2171 as a monotherapy were double that of standard care for this group.
- More updates on plans for Panzem (2ME2) at Duke, presented at ASCO 2007 (see also May 2007 article).
- A very short report from Italian researchers at the DIBIT Stem Cell Lab in Milan about a "stem cell switch" that can block the growth of malignant stem cells in gliomas.
- MGI Pharma reports on 2 glioblastoma studies at the ASCO 2007 meeting: one demonstrating prolonged survival in patients with Gliadel wafers implanted at initial resection, and the other reporting on Gliadel plus O6-benzylguanine (O6-BG) for patients with recurrent glioblastoma.
- Merck and Dr. Roger Stupp report results at ASCO 2007 of a study for newly diagnosed glioblastoma using concomitant cilengitide with standard temozolomide and radiotherapy treatment. The study yielded results significantly better than standard therapy alone, especially for patients with a methylated MGMT gene promoter.
- Duke researcher at ASCO 2007 discusses the role of molecular targets in glioblastoma stem cells.
- Mayo Clinic researchers report at ASCO 2007 that Vorinostat, an oral histone deacetylase inhibitor, shows survival benefits in treating recurring glioblastoma as a monotherapy. They will next combine Vorinostat with other drugs.
- A University of Rochester Medical Center study reports that modafinil (Provigil) helps enhance "cognitive function" in cancer patients suffering from an impairment of brain function after chemotherapy.
- Mayo Clinic researchers report success using ginseng to treat chemo-related fatigue.
- A study at USC reports that genistein and soy intake does NOT adversely affect levels of tamoxifen or its metabolites.
- Great initial Phase I results are reported at ASCO 2007 for a small molecule study drug called XL880 from Exelixis. While this trial involved a variety of advanced solid tumor patients, XL880 has demonstrated efficacy in vitro for GBM. XL880 inhibits VEGFR2 and MET (Mesenchymal epithelial transition factor), whose expression is often inversely proportional with glioma patient survival.
- University of Pittsburgh researchers discover that 4 of 5 glioblastoma patients have abnormal expression of a protein called integrin alpha 7 (a7). In mice, increasing the level of normal integrin a7 was associated with decreased tumor growth and metastasis.
- A UCLA glioma study showing that VEGF expression is "predictive of survival in tumors with little or no edema, but not in tumors with extensive edema." The study further demonstrates multiple pathways of edema production in gliomas.
Clinical Cancer Research. 2007 May 1;13(9):2592-8
PubMed ID: 17473188
- Entremed begins Phase 2 trial of Panzem + Temodar in GBM at the Duke University Brain Tumor Center. Panzem (2ME2) is a metabolite of estrogen which is both an anti-angiogenesis agent and an apoptosis inducer. Panzem is well-tolerated, but has produced only modest benefits as a monotreatment for GBM. It will hopefully be more effective as part of a drug cocktail.
- Researchers at Harvard report that the marijuana cannabinoid THC potently inhibits EGF in lung cancer.
- A new Phase I trial of a glioblastoma immunotherapy treatment has begun at Cedars Sinai in L.A. for newly diagnosed patients, using the dendritic cell-based vaccine from ImmunoCellular Therapeutics.
- More details on the presentation (see original post in Apr 2007 news) at the AACR concerning the excellent Phase II results for the pan-VEGF inhibitor AZD2171 (Recentin or cediranib).
- An initial report on NIH research using a hydrogel to deliver chemo drugs to glioblastoma resection sites, in situ.
- Interesting Canadian/U.S. research reveals a potential new "bioswitch" for glioma cell survival, in the form of G6PT gene expression, which can be modulated with a variety of existing substances.
Neoplasia. 2007 Apr;9(4):332-40
PubMed ID: 17460777 (full article!)
- Dana-Farber and Harvard Medical School report on a treatment protocol for recurrent glioma using a metronomic schedule of 4 different antiangiogenesis drugs and although the trial reported mediocre results, the recruited patients had largely failed prior treatments too.
Neuro-oncology. 2007 Apr 23
PubMed ID: 17452651
- Description of a newly discovered ligand, Lectin-like transcript-1 (LLT1), which is over-expressed in gliomas, and how it can be down-regulated by small interfering RNA (siRNA) to promote lysis (tumor cell rupture).
Cancer Research. 2007 Apr 15;67(8):3540-4.
PubMed ID: 17440061
- Another study demonstrating that thalidomide + temozolomide is not significantly more effective than temozolomide alone when used during or immediately after initial radiation treatment.
Anticancer Research. 2007 Mar-Apr;27(2):1067-71
PubMed ID: 17465245
- An update of ongoing research in Italy using photodynamic therapy to differentially kill GBM cells.
Clinical Cancer Research. 2007 May 1;13(9):2606-13
PubMed ID: 17471562
- A study indicating that "MGMT methylation is part of a genetic signature of glioblastomas that developed from lower-grade gliomas."
International Journal of Cancer. 2007 Apr 30
PubMed ID: 17473190
- An overview of genetic differences between primary glioblastomas, which account for 90% of GBM diagnoses, and secondary glioblastomas, which progress from lower-grade tumors.
American Journal of Pathology. 2007;170:1445-1453
- A new potential treatment for temozolomide-resistant glioma tumors by using adjuvant human tumor necrosis factor-related apoptosis-inducing ligand (hTRAIL).
Journal of Neurosurgery. 2007 Apr;106(4):646-51.
PubMed ID: 17432717
- An update on the immunotherapy treatment vitespen (a heat shock protein peptide complex-96 vaccine), brand name Oncophage from Antigenics, which is in trials at UCSF.
- News from the American Association for Cancer Research conference. Includes news on a new way to encapsuluate oncolytic measles virus in "blood outgrowth endothelial cells" to prevent them from being destroyed by the immune system; and an update on AZD2171, a pan VEGF inhibitor.
- Harvard School of Public Health finds that eating fruits and vegetables does NOT likely lower the risk of glioma.
American Journal of Clinical Nutrition. Mar 2007, 85(3): 877-86.
PubMed ID: 17344512
- UCSF details a novel new study drug called AN-113, a precusor of the parent drug 4-phenylbutyrate which has shown promise in a Phase I study. AN-113 can "efficiently kill glioma cells", is bioavailable and potent when orally administered, can cross the blood brain barrier, and has "effectiveness in combination with radiation."
Cancer Letters, Mar 6, 2007
PubMed ID: 17346876
- Protherics announces start of Phase I trial of OncoGel, a locally-administered, sustained-release formulation of paclitaxel, a widely used cytotoxin.
- NeoPharm's Cintredekin Besudotox (IL13-PE38QQR) treatment for GBM may be delayed by FDA, which requests another Phase III trial.
- Celldex's EGFRvIII-targeted immunotherapy treatment for GBM, developed by Dr. Albert Wong of the Stanford Comprehensive Cancer Center, begins new, larger trials based on solid success...
- Rexahn Pharmaceuticals announces that their first-in-class AKT protein kinase inhibitor, RX-0201 (Archexin), has been named to be among "100 Great Investigational Drugs" of 2007. Archexin has Orphan Drug status in the U.S. for glioblastoma treatment.