Glioblastoma multiforme grade 4 is the most common malignant brain tumor, accounting for 15.6% of all primary brain tumors. The median age of diagnosis is 59 years. Increase utilization of cranial imaging for headaches, seizures, and trauma has led to an increased diagnosis of tumors. Farmers and petrochemical workers have shown a higher incidence of brain tumors. Also, factors such as dental x-rays and ionizing radiation are causative factors. New evidence also suggests that the CMV virus is associated with glioblastoma. Many other viruses can cause cancer formation.

New personalized testing is now available including the analysis of your circulating cancer cells, chemo sensitivity testing, genetic driver mutations, and natural testing is available. Personalized genomic brain cancer testing and treatment has revolutionized the treatment of brain cancer.

The first occurrence in older patients with poor survival has several dysregulated driver mutations. These consist of the p53 pathway, the retinoblastoma Rb pathway, and the PI 3K pathway. A recent study in the cancer genome atlas found that the p53 pathway is abnormal. These mutations detected during new molecular genomic testing and biomarker testing.

Among the reasons for the reduced efficacy of chemotherapy and targeted agents is the low concentration of the drug penetration to the tumor because they cannot cross the blood-brain barrier. Also, resistance is an essential reason for the lowered efficacy of chemotherapy. Central to treating brain tumors is the issue of drug delivery through the blood-brain barrier (BBB).

I am using several modalities to increase the transfusion of therapeutics across the blood-brain barrier. Also many substances reverse drug resistance. It is vital because the blood-brain barrier is used by the body to block toxins and other harmful chemicals in the bloodstream from getting to the brain. Besides, cells here suppress the local immune system of the brain. There are an increasing number of T regulatory cells and myeloid suppressor cells, which block the effects of the anticancer immune cells protecting the tumor from being attacked. Treatments restores these levels.

Recent studies have shown that melatonin may inhibit the viability and self-renewal of glioblastoma cells. Melatonin affects cellular signaling pathways involved in cell survival, and it may block cells from invading new areas by inhibiting genes involved in tissue invasion and new blood vessel formation. In laboratory studies, melatonin boosted the effect of chemotherapy drugs, including temozolomide, which should be taken by all patients. Andrew natural substances also, the side effects of radiation are minimized and several patients taking melatonin. I suggest a high dose taken as tolerated by the patient. I am using it intravenously to obtain a maximal effect in all patients.

A new laboratory study also showed that vitamin D enhanced the toxicity of temozolomide against glioblastoma cells. It prolongs survival and reduces tumor progression. Green tea, curcumin, quercetin, and resveratrol have also shown to be effective. Some studies have shown that polyunsaturated fatty acids, such as DHA, are effective at reducing tumor progression.

New personalized cancer vaccines, including autologous cancer vaccines, dendritic cell vaccines, and supportive oligonucleotide therapies (SOT), are taken from the patient’s circulating cancer cell and made in the laboratory. They are then injected back into the patient’s bloodstream and go to the brain to kill the tumor cells. In addition, new research shows that the checkpoint inhibitors may also be useful when combined with therapies that can penetrate the blood-brain barrier (BBB).

The patient’s underlying immune system needs to be evaluated and optimized. As reported in the annual meeting of ASCO, a new vaccine against glioblastoma called SurVaxM demonstrated an encouraging efficacy. This vaccine was produced at the Roswell Park Comprehensive Cancer Center. It is a novel peptide bass vaccine that targets survivin, a tumor-specific antigen nearly universal in patients with glioblastoma. The patients who were treated had gene mutation MGMT. Genetic evaluation is extremely important. Other studies have looked at the EGFR gene and found them in glioblastoma patients. It is allowed for selecting specific chemotherapies and targeted molecules to target this gene. Again, genetic evaluation is important.

We are now able to analyze the genomics of your brain cancer through new molecular technology. We are now able to measure genetic markers and 72 related “biomarkers” that are used to personalize the treatment program. This further molecular testing offers early detection of brain cancer and personalized new treatment options. Chemosensitivity testing allows us to choose the chemotherapy that works and the natural substances that are effective.

Chemosensitivity testing is essential to determine which chemotherapy is most important and has the highest efficacy. Low dose metronomic chemotherapy, when used, allows for more frequent dosing with a minimal side effect profile. Low-dose chemo therapy will not suppress the immune system and has minimal toxicity and side effects. When the genetic and molecular pathways of brain cancers are better understood, and new targets identified, the inhibitors that attack the signaling pathways and making the brain cancer growth will be treated. We will also utilize the natural substances to reverse the resistance that causes brain cancer cell death. We consider this a personalized cancer treatment.

Solid tumor brain metastasis is increasingly common. Surgical resection and, or radiation can initially be effective, but new research using immunotherapy shows it to be useful. Brain cancers have decreased amounts of T lymphocytes, causing problems with immune therapies. Immune checkpoint inhibition using PDL-1 PD1, and CTLA–4 have shown remarkable results inhibiting brain metastasis. The checkpoint inhibitors are also being combined synergistically with radiation. Patient selection and biomarkers are crucial. Multimodal therapy is thought best.

Glioblastoma multiforme is characterized as having a high degree of hypoxia or low oxygen and is resistant to therapies because it adapts through autophagy. Autophagy is a process where there is degradation or breakdown of all the parts of the cell leading to the formation of new ATP and energy for the cancer cell. Unfortunately, this leads to her survival and resistance to many anticancer treatments. The good news is there is a way to block this and improve oxygen levels in the cancer brain cells.