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.)

HPV is not only limited to cervical cancer, but has also been implicated in squamous cell carcinomas of the head and neck regions (HNSCC) and includes oral, tonsillar, and oropharyngeal tumors—which have usually been associated with long term alcohol and tobacco usage. The incidence of HNSCC has risen steadily over the last 20-30 years in younger patients, and about 20% of these carcinomas are HPV positive with HPV type 16 emerging as the most prevalent subtype present in these tumors.

However, unlike the clinical regimen for cervical carcinoma which includes HPV typing of the tumor tissue, there are currently no standard molecular tests utilized as part of the clinical treatment protocols for head and neck cancers. Prognostic factors for survival include molecular diagnostic testing for cytokines, proteomic profiling, and testing for the presence of HPV.

Interestingly, the detection of HPV in  head and neck cancer is a favorable prognostic marker; HPV positive tumors are biologically distinct from HPV negative tumors which are typically associated with long-term tobacco and alcohol use. This favorable prognostic factor in younger patients with HPV positive tumors may be attributed to the lack of p53 mutations found in younger patients, and thus improves chemotherapeutic treatment response in these patients, in part because the efficacy of chemotherapy depends upon a functional p53 gene that mediates apoptosis (programmed cell death) in response to radiation and chemotherapy.

Note: the thumbnail above shows visibly HPV-infected cells