Researchers at the University of California Los Angeles and Ohio State University Comprehensive Cancer Center are investigating a new treatment for glioblastoma, the deadliest form of brain cancer. Their paper, out this week in Cancer Discovery, shows how blocking a mechanism involved in cell metabolism and triggered by a cancer gene can reduce brain tumors.

Glioblastoma affects about 18,500 Americans each year, with less than a third surviving. The brain tumors are very difficult to remove as the cancer cells invade surrounding brain tissue. To make matters worse, some people are genetically predisposed to resisting chemotherapy or radiotherapy.

The researchers looked at the cellular mechanism that involves an over-active PI3K signaling pathway. This pathway is stimulated by a gene variant called EGFRvIII, which is present in nearly half of all glioblastomas. The gene variant also switches on a transcription regulator, increasing the activity of the low-density lipoprotein (LDL) receptor. This increases the uptake of LDL, providing more cholesterol for the brain tumor cells to feed on, grow and survive.

The number of LDL receptors was reduced in these experiments by activating an alternative receptor, the nuclear Liver X Receptor. This then caused the cholesterol to be transported back out of the tumor cells using an ABCA1 protein pump. Without the extra cholesterol, the greedy brain tumor cells eventually starve and die.

The good news is that this signaling pathway is not just confined to glioblastomas so this therapy may eventually be used to treat other forms of cancer.

So it’s yet another reason to cut out the eggs, cream and butter and have oatmeal for breakfast!

Guo D, Reinitz F, Youssef M, et al. An LXR agonist promotes glioblastoma cell death through inhibition of an EGFR/AKT/SREBP-1/LDLR-dependent pathway. Cancer Discovery 2011; early online.

(For more on signaling pathways in cancer cells, check out “Pathways to Cancer” @ the Inside Cancer website.)

The point in mentioning these semantics is that the public is generally (kept?) unaware of how complicated the research process is, and how scientists who venture into discovering the unknown have to pick and choose their battles, making choices about how much or how many details they will pursue and at what cost.

It has been suspected for some time now that in Alzheimer’s the abnormal build up of plaques (formed by proteins called β-Amyloids) cause toxicity to neurons and damage the functioning of the brain. This finding was already a major step in fighting a devastating disease which is still poorly understood and which, not for lack of effort, has no satisfactory clinical intervention beyond attempts at early identification, some mildly successful drugs which may delay its onset, and general palliative care.

Recently, an investigation published here in the Journal of Biological Chemistry neatly illustrates how refined sleuthing can refine the instruments of inquiry available in the fight against Alzheimer’s and other debilitating diseases. The β -amyloid protein (APP) which has been the subject of previous study actually comes in three forms (APP₆₉₅, APP₇₅₁, and APP₇₇₀) which differ in the amino acid length of the protein. The work by Nikolai Belyaev et.al. demined that it this dangerous plaque is formed mainly by the APP₆₉₅ form which is found in higher concentration in brain and nerve cells. Identification of this particular APP isoform also explains the presence of another protein (AICD) which forms when the APP₆₉₅ isoform is broken down leading to activation of genes that further damage cells.

So why weren’t researchers focusing on this isoform before, instead choosing to study all three forms of APP (as if they were a single entity)? It’s a valid question. Was this negligence on anyone’s part? Mostly likely the answer is no. This new finding is simply the unfolding of the scientific process such as it is. For those who did the original work on looking at β -amyloid proteins, or any other proteins, there are only a limited number of questions that can be asked within a given time, given budget, or a given amount of accessible knowledge. Although the pace of research is in Alzheimer’s accelerating, the picture is never complete; pointed investigations like this one will continue to find gaps, and sharpen the focus as progress is made toward a cure.

In the fall of 2009, the World Health Organization published a 10 year study which examined the cell phone habits of more than 120,000 people in 13 countries. The study reported a significantly higher risk of developing brain tumors in individuals with 10 years or more of cell phone usage. Similar findings in other studies have added to the growing concern over long-term exposure to cell phone usage.

In 2007, Dr. Lennart Hardell, from Örebro University in Sweden, reported an increased risk of malignant glioma in cell phone users, and that a daily one hour exposure significantly increased the risk for developing a brain tumor after 10 years. Recently, Dr. Ronald B. Herberman, director emeritus of the University of Pittsburgh Cancer Institute delivered a memo to over 3000 staff and faculty members, essentially warning them of the health risks of cell phone use, and specifically stated that children should limit cell phone use to emergencies only.

So why aren’t cell phones packaged with health warning labels in the same way that alcohol and cigarettes are labeled? The jury is out on whether the cell-phone and brain tumor link is convincing enough to warrant major concerns. In fact, the number of studies that render the link inconclusive far outnumber the studies which do (arguably, though, we can exclude studies funded by telecommunication companies). Discrepancy in these findings is due in large part to the inherent bias found in case-control studies, which are designed to examine specific factors that may contribute to a disease process or illness by comparing similarly matched individuals, those with and without the medical condition in question. In this case, the studies essentially rely on the participant’s recall of cell phone usage patterns as far back as 10 years.

Further substantiation of the clinical health risks posed by cell phone usage will need to include cohort studies, where healthy individuals, with and without exposure to cell phones are followed over a period of time and examined for occurrence of brain tumors. This of course means that it will take years to adequately determine the health risk. In the meantime, it may serve us well to heed recommendations to limit exposure to the electromagnetic radiation emitted by cell phones.

References:

http://artpredator.files.wordpress.com/2009/03/cell-phones-on-planes.jpg

http://www.webmd.com/cancer/brain-cancer/news/20091203/cell-phones-and-brain-tumors-no-connection

http://www.ncbi.nlm.nih.gov/pubmed/17409179

http://www.post-gazette.com/downloads/20080722upci_cellphone_memo.pdf

http://www.cancer.gov/cancertopics/factsheet/Risk/cellphones

http://www.medicalnewstoday.com/articles/161960.php

http://www.reuters.com/article/idUSTRE59C5GA20091013

http://www.newser.com/story/69023/report-revives-fears-of-cell-phone-tumor-link.html

http://www.physorg.com/news175853675.html

Cancer cells have mutations in their genes that render them unable to respond to signals that regulate cell division. These cells grow uncontrollably and can invade normal tissue in other locations of the body and cause disrupted functions of major organs. This is why cancer is so deadly.

A mutagen is a physical or chemical substance that can alter genetic material in cells. DNA can be damaged or changed (mutated). Cancer cells have changes in the genes themselves. These changes can include mutations , deletions of part or whole genes or even the addition of extra copies of genes.

There are many mutagens that can cause cancer in cells. These are called carcinogens. Two of the most common and most deadly cancers, lung and skin are caused by two well known carcinogens, cigarette smoke and sunlight. Some studies suggest when 15 cigarettes are smoked, an error in DNA occurs.

Now the UK’s Wellcome Trust Sanger Institute has cracked the code for the mutations within DNA that can cause tumors that lead to these two devastating types of cancers.

This new information can open the door to major advancements in treatment, medication and maybe even cures in the future of skin and lung cancers.