The genome and glioblastoma

The Cancer Genome Atlas Project is an NIH-sponsored program to systematically catalog the genetic alterations in human cancers. The first cancer type investigated is Glioblastoma multiforme (GBM), the most common and most aggressive form of brain cancer.

http://cbio.mskcc.org/cancergenomics/gbm/

The Cancer Genome Atlas (TCGA) group has recently discovered that there are actually 4 genenic types of glioblastoma multiforme and that this information might help in figuring out why some clinical trials work for some patients but not all patients

http://www.nih.gov/news/health/jan2010/nci-19.htm

http://www.massgenomics.org/2010/01/subtyping-glioblastoma-via-genomic-analysis.html

Now that the genome for this cancer has been mapped, scientist can use this information to help develop targeted gene therapies.  For example : \

Further statistical analysis of the TCGA data revealed that miR-26a likely inhibits, or targets, three tumor suppressor genes called PTEN, RB1 and MAP3K2/MEKK2.  These genes are frequently mutated in many other cancers.  The researchers guessed that miR-26a aids GBM development by turning off these tumor suppressors.

http://cancergenome.nih.gov/researchhighlights/researchbriefs/microRNAGBM

Promising Treatments

The standard treatment for glioblastoma does not give patients much hope however I believe there is real promise on the horizon.    These are some of the directions of research and clinical trials that I have found interesting:

1) Dendritic Cell therapy – Targeting tumor-associated antigens with dendritic cells may be an effective way to combat GBM.  ICT-107 is an immunotherapy in which the patient’s immune response will be stimulated to kill the tumor cells.

http://www.imuc.com/imuc-09-07-2011

http://www.medscape.com/viewarticle/719907_4

http://www.jibtherapies.com/content/9/1/1

2) Autologus Cell therapy: Some immunization protocols use autologous cells that have been genetically modified to render them more immunogenic, for example, IL-4-transfected fibroblasts, B7-2 and granulocyte-macrophage colony-stimulating factor-transfected tumor cells or glioma cells infected with the Newcastle disease virus

3) Combined gene therapies: studies show that the majority of rats bearing large tumors were still alive six months after combined treatment with two proteins: RAdTK, a protein that kills cancer cells, and RAdFlt3L, which stimulates immune or dendritic cells in the brain

http://www.medicalnewstoday.com/releases/29141.php

4) Ketogentic Diet as an adjunct therapy –  The ketogenic diet is used commonly to treat refractory epilepsy in children and, when administered in restricted amounts, can also target energy metabolism in brain tumors.  This metabolic deficiency allows the tumor cells to be metabolically isolated from normal cells. A strong dependence on glucose makes the tumor cells vulnerable to death using therapies that target glucose metabolism. The ketogenic diet, administered in restricted amounts, is ideally suited as a non-toxic metabolic therapy for managing malignant brain cancer because the diet naturally lowers circulating glucose levels while elevating levels of ketone bodies

http://www.nutritionandmetabolism.com/content/7/1/33

Prognosis

Lets just say it isn’t great but there is no sense putting a number to it for the following reasons:

  1. She is young which will work in her favour for being able to tolerate the treatments
  2. She has no other medical issues that might complicate treatment
  3. The surgery was very successful and hopefully removed 99% of the tumor which was large
  4. The standard numbers for prognosis are based on results that are several years old.  With new treatments, it takes several years for the prognosis numbers to reflect these improvements
  5. Radiation treatment is improving rapidly as new equipment and methodology comes to the market
  6. The prognosis numbers do not include results of clinical trials

 

 

What is Glioblastoma Multiforme

http://www.braintumor.org/patients-family-friends/about-brain-tumors/tumor-types/glioblastoma-multiforme.html?agclid=COCfu_6ypakCFUa8KgodljMbyA

According to the National Brain Tumor Society…

An astrocytoma is a glioma that develops from star-shaped glial cells (astrocytes) that support nerve cells.  A glioblastoma multiforme is classified as a grade IV astrocytoma.  It is also referred to as a glioblastoma or GBM.

 
Characteristics

  • Most invasive type of glial tumor
  • Commonly spreads to nearby tissue
  • Grows rapidly
  • Includes distinct genetic subtypes
  • May be composed of several different kinds of cells (i.e., astrocytes, oligodendrocytes)
  • May have evolved from a low-grade astrocytoma or an oligodendroglioma
  • Common among men and women in their 50s-70s
  • More common in men than women
  • Accounts for 17 percent of all primary brain tumors

 
Treatment

 
Standard treatment is surgery followed by radiation therapy or a combination of radiation therapy and chemotherapy. If surgery is not an option, the doctor may administer radiation therapy followed by or in conjunction with chemotherapy. Many clinical trials (experimental treatments) using radiation, chemotherapy, or a combination are available for initial and recurrent GBM. Clinical trials using molecularly targeted therapies showing success in other cancers are also being tested in GBM patients.