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.

Nanotech Blood Pressure Monitor


Coming soon to your body: A real-time blood pressure monitor.

As discussed in the article Nanowires in the blood could feel the pressure, reseachers at the Georgia Institute of Technology used the piezoelectric effect in zinc oxide semiconducting nanowires to generate a current proportional to the amount the nanowire is bent. When implanted in the body, a change in blood pressure could easily be monitored by a device using this sensitive technology (detection of forces at the piconewton scale: 10^-12 N). Zinc oxide is also biocompatible, so it is very unlikely to be attacked and rejected by the immune system.

Get ready for a variety of devices that could interact with this sensor, as it could relay information through a simple wireless signal. Just think of the number of other biological applications this could have. Brain pressure sensing in concussion patients? Researchers are constantly developing new nanoscale, biocompatible sensors, generators, switches and transmitting systems. This nanowire pressure sensing device will surely be added to the biosensing and reporting toolkit.

Some nano toolkit links:

Stem Cells: A day in Review


There has been a flurry of activity today with headlines discussing all sorts of findings with relevance to stem cells. In this post, we are going to discuss finding a muscular “fountain of youth” switch, a successful stem cell therapy in mice (we’ve cured so many mice), and the potential discovery of a true stem cell in breast cancer.

Dr. Elena Vasyutina, Carmen Birchmeier, and Diana Lenhard of the Max Delbrück Center for Molecular Medicine (MDC) found a genetic switch (RBP-J) that governs the regeneration of satellite cells (muscle stem cells) . If this switch is turned off, satellite cells decrease in overall number, and are replaced by normal muscle cells which will ultimately die and become unrenewable over time (aging?). See Fountain Of Youth: Molecular Switch Holds Key To Reserve Supply Of Muscle Stem Cells for a full review on the research findings.

In other news, doctors at the Burnham Institute for Medical Research found that stem cells act through multiple mechanisms to benefit mice. The article mentions that the scientists were successful at implanting mouse neural stem cells (NSCs). These stem cells replaced damaged brain tissue and were found integrated throughout the brain. In fact, some transplanted cells transmitted nerve impulses, which showed electrical integration and functionality in a previously diseased brain. This is potentially great news for patients with ALS, Alzheimer’s and Parkinson’s disease. A stem cell therapy might be just around the corner.

The March issue of Cancer Cell reports that a group of scientists, led by Dr. Kornelia Polyak of the Dana-Farber Cancer Institute, that there are two genetically distinct tumourigenic breast cancer cells. Dr. Polyak said that “If the breast cancer cells were all coming from a single cancer stem cell, you might be able to cure the disease with just one drug. But our findings suggest that the tumor cells come from a ‘stem-like’ progenitor cell, and then diverge genetically, so I think you have to treat both cell types.” (See full story by harminka, writer at HULIQ.com)

India Update: Finance Bill 2007


Some changes are going to happen in the finance communities in India. Their Finance Minister, Palaniappan Chidambaram, recently presented the Finance Bill 2007. PricewaterhouseCoopers put out an extensive report discussing the implications for Ireland, but also discusses many of the changes affecting overseas investments among other tax and investment changes.

India’s venture capital scene is highlighted by a tax pass through status eligible to foreign and domestic funds, as discussed in The Financial Express. What does this mean? It means that they are exempt from tax on income from investments in venture capital undertakings. However, this is not the case for all industries. This tax pass through is only applicable to investments in the IT, biotech and nanotech industries.

Another article in The Financial Express highlights a new clause put into Finance Bill 2007 surrounding gas distribution networks.

“A new clause (vi) inserted in sub-section (4) of Section 80-IA provides that any undertaking carrying on the business of laying and operating cross-country natural gas distribution network, including gas pipelines and storage facilities being an integral part of the network, will be eligible for deduction under the section if it is owned by a company registered in India or by a consortium of such companies or by an authority or a board or a corporation established constituted or constituted under any Central or state Act…” (Full text available at The Financial Express)

It isn’t surprising to see the Indian government giving special provisions to gas distribution networks. At the rate business enterprise and consumer wealth is growing in India, much more energy is needed; a more comprehensive network of gas distribution will be required to get the energy where it needs to go. This is backed by a huge demand in automotive vehicles. A news report from Hindu Busines Line mentions that Hyundai Motor India realized a 74% increase in domestic vehicle sales during February 2007 compared to the same month last year. This is complemented by a 60% increase from Honda Siel Cars India (HSCI), and an 81% increase from General Motors. Nice trend. Where are you putting your money?

Want to learn more about doing business in the new Indian economy, consider a few bestselling books to gain some insight:

Put yourself in the know so that you can make the most of your investment strategy whether you’re a day trader, a fund manager or an average joe.

Global Warming, Cleantech and Canada


The world is ranting about global warming, and it should be. There is a very real problem, and finally politicians are appearing to try to combat them. Is their rationale money, power, influence or an actual regard for the sustainability of Earth?

In recent news President Bush announced an Ethanol deal with Brazil, which will work to increase the development of ethanol; Brazil produces much of its ethanol from sugar cane. Also today, the European Union heads of state agreed on a long-term strategy on energy policy, which followed agreements made in February 2007, when they agreed to cut greenhouse emissions by 20% by 2020. In Canada, Prime Minister Stephen Harper says that Kyoto targets are unattainable, as the former Liberal government committed to a reduction of greenhouse gases to 6% below 1990 levels … Canada is currently 35% over that mark (Vancouver Sun). So … what is Canada going to do to address this issue? Maybe allocate an increase to the investments in startups that are focusing on environmental biotechnology or cleantech solutions? Wow, that sounds like a good idea!

There are currently a number of Canadian company developing cleantech technologies, but certainly not enough. Of those companies innovating that space, most are grossly underfunded as many don’t even have websites! As the Toronto Star tech reporter, Tyler Hamilton, mentions in his cleantech blog – Clean Break – Sustainable Development Technology Canada (SDTC) , a fund created to finance cleantech startups, invested only $43.4 million on 15 new projects in 2005. The Alberta government is currently experiencing massive surpluses in the order of billions, its about time to start financing cleantech and environmental biotech startups so that Canada can remain competitive in the energy, or “Clean Energy” space in the future. Getting an early foothold in the market just seems like a good idea to me …

Canadian technology happens to be some of the most innovative in the world, so says Len Brody, who’s keynote address I saw at the Canadian Venture Forum. Nice guy, I managed to get myself a signed copy of his book Innovation Nation: Canadian Leadership from Java to Jurassic Park. I haven’t had a chance to read it yet, but if your patriotic and want to find out a little more about Canadian business … maybe grab yourself a copy. In any case, if Canadian technology is so innovative, then INVEST IN IT. The lack of funding at the early stage, is crippling the growth and development of Canadian companies. CEOs are constantly chasing money, to stay cashflow positive and burn rates are minimized, which doesn’t allow these start-ups to effectively execute on their business plans.

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.