Glioblastoma multiforme (GBM) is the most prevalent adult malignant brain tumor and has dismal survival rates despite standard treatment approaches such as surgery with concomitant chemotherapy with temozolomide.
Brown University researchers claim a derivative of indirubin offers new hope for GBM patients. Their drug was discovered through research in mice and works against cancer cells through multiple mechanisms.
Boswellia
Boswellic acid is a key constituent in the oleogum resin of Boswellia trees, which grow across India, North Africa and parts of the Middle East. Farmers tap these trees to harvest this resin – known as Frankincense in common parlance – which farmers then tap for use as incense or use it themselves for incense-making purposes. Natural health practices have utilized the plant for centuries while scientific research is now revealing some potential advantages associated with it.
Boswellic acid may offer great promise in treating inflammation-based health conditions such as arthritis and asthma, specifically its use for joint and asthma symptoms. It contains compounds which reduce inflammation, while studies also suggest its ability to alleviate pain from arthritis. Research suggests it could even prevent leukotriene formation that contributes to inflammation-based autoimmunity responses.
Additionally, this herb has the power to ease bronchitis and asthma symptoms by inhibiting leukotriene production, which causes bronchial muscles to constrict and increase mucus secretion in people living with asthma. Furthermore, its compounds could block Th2 cytokines which promote inflammation causing bronchitis; one small study demonstrated how Frankincense reduced inhalations treatments required by asthmatics.
Researchers attribute Boswellia’s anti-inflammatory benefits to its ability to block certain enzymes and alter how certain chemical signals are released by cells, preventing inflammation responses that damage DNA and contribute to cancer formation, slowing leukemia progression and other tumor growth, or limit spread of existing cancer cells.
Though further research needs to be completed, boswellic acid appears to possess an impressive safety record. When taken orally or applied topically in amounts typically found in food, it should likely be safe; however, large doses could potentially cause stomach ache, nausea, diarrhea, heartburn and general weakness. It might interact with several medications including those metabolized by the liver; additionally it should not be taken by pregnant or breastfeeding women.
Supplements come in various forms, such as capsules, tinctures, tablets and gels. You can find them both online and at natural health stores; dosage varies based on manufacturer instructions so always consult your physician first before starting to take them.
Indirubin
Indirubin, a natural product found naturally within the human body, has many therapeutic applications that include inhibiting cancer cell growth and activating leukemia cell apoptosis processes. Indirubin works by binding to its target xenobiotic receptor AHR which triggers downstream genes such as Cytochrome P450 1A1.
Studies on Indirubin have demonstrated its effects against cyclin-dependent kinases and GSK-3b. Additionally, its activities target mitogen-activated protein kinases (MAPKs), nuclear factor kappa B (NF-B) and JAK/signal transducer and activator of transcription 3 (STAT3); these activities make indirubin an attractive candidate drug candidate in treating cancer and other diseases. Indirubin derivatives have been developed that are more effective inhibitors with unique binding models inside their ATP binding pockets; making these derivatives superior than canonical Indirubin canonical counterpart.
Indirubin induces apoptosis in tumor cells by downregulating anti-apoptotic proteins while upregulating pro-apoptotic proteins such as bax, bak, and caspase 3. Additionally, indirubin increases bcl-2 expression while simultaneously suppressing expression of c-MYC, an important regulator of cell proliferation.
Indirubin also reduces phosphorylation of ERK and mTOR, blocks signaling pathways mediated by JAK3/STAT3 and reduces secretion of proinflammatory cytokines; its anti-inflammatory effects have been seen in various models such as imiquimod-induced psoriasis and lipopolysaccharide-induced mastitis.
Recent findings of a new study indicate that Indirubin may help treat glioblastoma in mice. The research was carried out at Memorial Sloan Kettering Brain Tumor Center under developmental biologist Luis F. Parada and revealed that Indirubin significantly reduced viability of GBM cells while simultaneously inducing their apoptosis; additionally it has also been proven to accelerate wound healing within mouse skin. Efficacy improvements of Indirubin will still need to be investigated before use clinically;
Gallium Maltolate
Gallium maltolate (GaM) is a therapeutically useful compound. As a trivalent form of gallium, GaM binds with various coordination ligands to prevent its toxic hydroxide form from forming and harming cells. GaM also exhibits antiproliferative and antineoplastic effects, and has been proven to suppress DNA synthesis, promote cell death, induce apoptosis in cancer cells, improve bone resorption and help protect against osteoporosis. Research has demonstrated that gallium maltolate can substantially lower levels of pro-inflammatory cytokines such as TNF-a and IL-6. Furthermore, gallium maltolate increases tumor permeability to allow excess blood from tumors to escape through extravasation, ultimately leading to decreased blood pressure – beneficial for people living with heart disease.
Studies have demonstrated the use of gallium ions to treat glioblastoma, a form of brain cancer. Researchers observed that gallium bound to transferrin receptors within cancer patients’ brains to disrupt iron metabolism, thus stopping its spread to stop growth of tumors such as glioblastoma or other brain cancers. Clinical trials for the therapy are ongoing and it appears promising for treating patients living with this form of brain cancer.
Gallium ions not only offer anticancer benefits, but they can also be used to protect the liver against damage from chemotherapy. They may even help prevent drug resistance. Gallium Maltolate may help ease hypoxia in hepatocellular carcinoma patients – this is an invaluable asset considering this form of cancer is one of the deadliest, with limited available therapies.
Gallium cations can interact and compete with iron for many key biological reactions, and do not need oxygen for oxidation – making them an excellent candidate for cancer therapy and other diseases. In addition to antiproliferative and antineoplastic effects, gallium compounds have also been proven to stimulate bone resorption while inhibiting cancer metastasis spread to bones as well as reduce activity associated with pain receptors such as metalloproteinases or neuropeptides.
Optune
Optune is an innovative new treatment for glioblastoma that uses Tumor Treating Fields (TTF) to slow its progression. Worn on the head, this device emits low-intensity electrical fields known to target cancerous cells without harming healthy brain tissue – perfect as an adjunct therapy alongside chemotherapy or surgery treatments.
Clinical trials demonstrating the Optune device have demonstrated it can improve overall survival compared to standard temozolomide alone. By adding Optune to one’s treatment regimen, adding Optune may significantly delay progression and increase survival; additionally it can help prolong survival for those suffering recurrent glioblastomas that originate in adult neural stem cells or oligodendrocyte progenitor cells.
This device is small and lightweight at only 2.7 pounds, offering patients the freedom to continue with daily routines while receiving treatment. Most patients who tolerated the device experienced only skin rashes near it that can easily be addressed; its design also allows it to be worn for long periods.
In the EF-14 trial, 51% of patients who received Optune reported continuing use after progression; however, it remains to be seen if this trend will hold true in clinical practice. Clinical experts consulted by CADTH were generally skeptical regarding claims of long-term survival benefit touted by Optune’s sponsor.
Optune’s effectiveness depends on a number of factors; in particular, those with skull defects or implanted electrical devices like pacemakers or defibrillators should avoid it. Furthermore, this device could interfere with other forms of brain imaging tests, including MRI or CT scans.
The EF-14 trial was a multicenter, open-label randomized clinical trial which enrolled 695 patients with ndGBM. Patients were randomly assigned to either Optune or temozolomide alone for 24 months as their treatment, and primary endpoints included PFS and OS, radiologic response, HRQoL as measured using EORTC QLQ-C30 questionnaire were important outcomes of this research project.
