New Pre-Cancer Biomarker Found

MIT scientists just discovered the function of 14-3-3 sigma protein, and also, what happens if it isn’t present in cells. This is a HUGE discovery toward preventative measures in cancer screening technology. It won’t be long before there are a new set of diagnostics out that screeen for a wide range of cancer precursor biomarkers that increase risk of cancer to a give tissue.

So, what do scientists propose that 14-3-3 sigma does? It plays a role in cell division. Specifically, it helps cells finish cytokinesis and separate into two distinct cells, right at the end of cell division. Michael Yaffe, an associate professor of biology and biological engineering and leader of the research team said “The cells try to divide and try to divide, and they just give up. They can’t finish cytokinesis.” This results in a single cell with two nuclei.

Key information not to be missed from the article:

  • Fused, or binucleate, cells have recently been shown to be precursors to cancer cells. They are often found in so-called “dysplastic” tissue, which consists of cells that are not fully normal but are not cancerous. Comparing tumors to weeds, Yaffe explained that those tissues act as fertile “soil” for tumor development. “Tumors grow in epithelial tissues that are already deranged for some reason, and something about that soil makes it better able to grow weeds.”
  • Loss of 14-3-3 sigma in dysplastic tissue could serve as a marker to help doctors predict whether tumors will develop. “Our hope is that it will be possible to monitor 14-3-3 expression in these ‘benign’ conditions, a subset of which may not be so benign,” said Yaffe.
  • The researchers were initially intrigued by the fact that 14-3-3 sigma is missing in normal tissue that surrounds tumors, which suggested that its function is lost very early in tumor development. Once the researchers started investigating the protein, they eventually unraveled a complex signaling pathway whose disruption leads to the failure of cell division.
  • They discovered that 14-3-3 sigma is most active during mitosis, when it helps control production of proteins necessary for division.
  • 14-3-3 sigma interacts with a translation factor known as eIF4B, whichforms part of an enzyme that allows mRNA to unwind so the ribosome can read its sequence.
  • When 14-3-3 sigma is knocked out, eIF4B is not produced, and mRNA for the protein p58 cannot be translated. p58 plays a critical role in the final splitting of one cell into two during mitosis, so when it is missing, the cells cannot fully divide.
  • When p58 function is restored, the cells resume normal division.

    The story was orginally issued by MIT, and covered by ScienceDaily under the title: MIT Identifies Role Of Key Protein In Tumor Growth

Pharmacogenetics Era: Cancer and Opiate Updates

Pharmacogenetics has “been around since the 1950’s” but, practically speaking, is a new player in clinical diagnosis and treatment, but it is changing the way that healthcare systems, pharmaceutical companies and even small biotechs position themselves in terms of developing new ways to combat disease. With DNA sequencing dropping in price by orders of magnitude, approaches to medicine are in the process of change. Now we are able to start at the genetic level, find out your genotype for a given gene and then recommend certain drugs to you based on your personal genetic profile.

Traditionally, most pharmacogenomic profiling existed with patients needed blood thinners, specifically warfarin, where the Cytochrome P450 gene was tested to determine its presence, mutations and copy number. These features let the physician know your relative rate of metabolism to see how you will respond to the drug and what dosage you should be taking. There are a number of other cytochrome genes that are often included in pharmacogenomic tests now, such as Cytochrome P450 2C9, which is an enzyme that metabolizes coumadin.

I found two examples recently that speak to some advances made in pharmacogenetics:

The first article discusses a new diagnostic called Oncotype DX which looks at DNA of the breast cancer cells to determine if the cells are benign, malignant, or metastatic. The test is commercially available and looks at 16 tumourigenic genes to determine how the cancer is going to behave. This is the tip of the iceberg for the cancer diagnostic market. Look out for more of these test as they are bound to pop up all over the place within the next 2 years. Mark my words.

The second advance is a Nature paper from Clinical Pharmacology & Therapeutics titled Pharmacogenetics of Opioids. They are looking at a number of genes, that, when present or absent, affect a persons dosage requirements. A selection of the article abstract is seen here that speaks to what the paper’s findings indicate:

The polymorphic CYP2D6 regulates the O-demethylation of codeine and other weak opioids to more potent metabolites with poor metabolizers having reduced antinociception in some cases. Some opioids are P-glycoprotein substrates, whereas, ABCB1 genotypes inconsistently influence opioid pharmacodynamics and dosage requirements. Single-nucleotide polymorphisms in the mu opioid receptor gene are associated with increasing morphine, but not methadone dosage requirements and altered efficacy of mu opioid agonists and antagonists. As knowledge regarding the interplay between genes affecting opioid pharmacokinetics including cerebral kinetics and pharmacodynamics increases, our understanding of the role of pharmacogenomics in mediating interpatient variability in efficacy and side effects to this important class of drugs will be better informed.

The pain market is large and vast, with 100-150 million Americans (~57%) having acute and/or chronic pain within the past year. Beyond America, over 500 million cases of pain are diagnosed worldwide each year, and most patients are unsatisfied with current treatment options. The worldwide pain management market symbolizes an escalating trend, having a value of $27 billion in 2004, with an expected increase to $35 billion by 2009. The number of people affected by pain, and have access to pain treatment is likely to escalate with the “baby boomer” generation approaching older age. Also, there is a trend indicating higher incidences of cancer, arthritis, HIV as well as surgeries[1].

There will undoubtedly be the need for advanced pharmacogenetic testing platforms that can determine the drugs that will work best for each individual’s pain need. Be sure to see these diagnostics enter hospitals and genetic labs in a few years!

[1] Frost and Sullivan. (2002) U.S. Pain Management Pharmaceuticals Markets.

Hey Cancer, We Can See You!

Two recent articles discuss diagnostic and medical imaging technologies that help researchers to identify cancers and look deep within. Another discusses some “preventitive medicine” that has no prevention, only costs.

Headlines indicate that Holographic Images Use Shimmer To Show Cellular Response To Anticancer Drug, and another study demonstrates that PET Imaging Identifies Aggressive Kidney Cancers That Require Surgery. The Holographic imaging research is at the cutting edge of technology, specifically, it is “the first time holography has been used to study the effects of a drug on living tissue,” mentions David D. Nolte. He is the leader of the research group from Purdue.

Some smokers and/or lung cancer candidates have been screened for presence of tumours or micro-tumours in the lungs by multi-detector CT scanners. While the technology found 3 times the amount of tumours than expected, earlier treatments for these patients didn’t yield better results as the mortality rate remained the same. Dr. Peter Bach, who is a lung physician and epidemiologist, and the study’s first author said, “Early detection and additional treatment did not save lives but did subject patients to invasive and possibly unnecessary treatments.”

But, Dr. Bach … you should focus on the fact that you were able to find 3 TIMES the amount of tumours originally predicted. Right now, current treatment regiments don’t allow for an increase in the number of lives saved, but as technology improves and more clinical trials come to market, many of these micro-tumours will be stopped in their tracks by new therapeutics, chemotherapies, cancer-targeting viruses, or perhaps nanoparticles linked to toxins which target tumorigenic tissues. Maybe the process of surgical excision should be rethought; maybe only certain tumours that have a certain genetic profile should be removed early. Genotype the tumour, and THEN deploy the necessary tactics. Don’t just cut out anything that looks like it “could” be fatal, surgeries often have complications and implications for the patient’s health.