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Cancer's Achilles Heel in the Crosshairs

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Cancer's Achilles Heel in the Crosshairs

The stubborn nature of cancer is legendary.  As years go by researchers, drug companies, and investors alike have searched for the source of a magical cure.  To date results are mixed at best.  While some treatments have shown remarkable progress in extending the lives of patients, extending the lives of patients with metastatic cancer remains substantially unchanged in major disease areas. 

Lung cancer is the leading cause of cancer death for both men and women worldwide.  Each year more people die from lung cancer than from breast, prostate, melanoma, and colon cancer combined.  Given that, lung cancer obviously would appear to be the biggest target for finding a cancer treatment or cure.  However, the overall 5 year survival rate for the disease has not really changed in decades.  The overall 5 year survival of lung cancer in the U.S. has been hovering around 15% since the war on cancer was declared by Richard Nixon in 1971.

Despite numerous advances in drug research and biotechnology drugs available for cancer treatment, there has been virtually no real progress in increasing life when patients are facing the #1 cancer killer.

By contrast, significant advancement has been made in several other areas.  Survival rates for metastatic colorectal cancer patients have increased substantially over the past few years.  Still median overall survival is only about 2.5 years up from about 14 months a decade ago.  The 5-year survival rate of metastatic colon cancer is up more than 100%.  Of course in reality that means going from around 9% to around 19%.  This is substantial progress and perhaps substantially disappointing at the same time.  However, investors in Genentech (a company long featured in our CurrinResearch.com portfolios) have reaped the benefits from the company advancing drugs that have helped improve the current outcomes.  The next batch of data for colorectal cancer is likely to show 5 year survival ticking up close to 30%.  But a 19% or even a 30% five year survival is certainly not the end game for a cure.  Indeed, either is far from it.    

"Cancer is a disease of the genome"

Dr. Francis Collins, Director of the National Institutes of Health

Much of the long frustrating experience with the war on cancer was a failure to recognize the genomic nature of the disease.  However for many years conventional chemotherapy served a genomic role by result rather than by design.  That is, conventional chemotherapy often served to destroy a cells ability to reproduce DNA necessary for reproduction and growth.  Unfortunately this occurs at great cost to healthy cells because chemotherapy does not discriminate between healthy cells and cancer cells.  The role of conventional chemotherapy is basically to kill cells.  It just happens to be that because cancer cells are reproducing faster than normal cells chemotherapy will kill more cancer cells than healthy cells.

Enter a genomic drug

Breast cancer has seen meaningful progress without a complete cure.  In fact, the methods of achieving progress in breast cancer and colorectal cancer are one of the central investment themes of our newsletter.  This is reflected in our Cell Signaling and Cancer Stem Cells portfolio.  Certain types of cancer, from the standpoint of the human genome, have been attacked quite successfully by using drugs specifically targeted to a genetic signature present. 

For example Genentech's drug Herceptin is effective when breast cancer patients are over expressing HER2 (Human Epidermal growth factor Receptor 2).  The drug Herceptin specifically inhibits the HER2 protein expressed in about 20 - 25% of breast cancer patients.  



Source: gene.com

 

A molecular diagnostic test is used to determine if a patient has elevated HER2 protein levels or gene copy number to determine if Herceptin will be a benefit.  Thus Herceptin is also an example of (and often cited as a pioneering example of) personalized medicine.  The patient's genetic test is used to determine if the correct drug is being applied.  Dramatic improvements in patient outcomes have been achieved in HER2 positive breast cancer.  Herceptin opened the door to treating cancer as a genomic malfunction disease...a disease of the genome.   

Herceptin targets one of many potential genomic aspects of cancer.  In the near future the genomics of the cancer will drive the therapeutic decision much more consistently.  We believe this gives investors substantial opportunity to capitalize on the intersection of the genome with cancer drug development and market potential.  Understanding this intersection and how it will significantly change in the next several years is key to maximizing your investment success in biotech.

"I would hope in another five years that we would have the capability to have the genome of your tumor completely analyzed-and then go through the list of drugs that are available"

Dr. Francis Collins, Director of the National Institutes of Health

Genentech's Avastin is example of a drug that targets a cell signal.  Avastin inhibits the pathway signaling responsible for rampant blood vessel formation to feed tumor growth.  This gives the drug a broad array of cancer indications and is the reason Avastin is such a blockbuster drug.  Genentech/Roche notched sales of nearly $6 billion for Avastin in 2009.

Our Cell Signaling and Stem Cell portfolio focuses on companies with key drugs in various stages of development in cell signaling.   We believe we have identified key developments with major therapeutic potential.  Our focus is on stocks with high potential for large returns.  We are also extremely excited about the major breakthroughs and profit potential about to occur in Cancer Stem Cells.

Cancer Stem Cells

...the root of metastatic potential is the Achilles heel of cancer

The basic hypothesis of cancer stem cells is that there are fundamental cancer initiating cells that promote a tumor response in other cells.  These cancer stem cells lead to recurrence and metastasis even when all signs of the cancer have been removed by surgery or conventional chemotherapy.  

csc

(Source: Macrogenics)

The bottom path of the above illustration graphically illustrates this process.

The Cancer Stem Cell Dilemma

Cancer stem cells (sometimes called mother cells, or tumor initiating cells) are resistant to traditional chemotherapy and radiation.  This creates a difficult problem in that the percentage of tumor initiating cancer stem cells actually rises relative to healthy cells after chemotherapy and/or radiation.  Thus the table is actually set for continuation or acceleration of disease after certain treatments despite having knocked down or even eliminated existing tumor cells.  There is even evidence that surgical removal of tumors actually promotes the cancer stem cell tumor response setting the stage for later relapse. 

One can think of this problem as using herbicides to kill weeds that do not actually kill the roots of the weeds.  Some of the lawn (healthy cells) may also die with the herbicide but the roots of the weeds are ready to re-propagate.  In addition the weed roots have been fertilized and now have less healthy lawn to compete with to block their re-growth.   That paints quite a picture of why the 5 year survival of lung cancer may not be changing very much.  With the right CSC drug candidates working their way to late stage clinical we believe this is about to change.

The cancer stem cell dilemma thus places the elimination of cancer stem cells and/or their ability to generate through pathways as crucial if not mandatory for ever getting to the root issue of metastasis and relapse.  In our Cell Signaling and Cancer Stem Cell portfolio we feature promising drug companies leading the way to eliminating the root cause of cancer relapse by attacking the genetic response to cancer stem cell proliferation of cancer.

Cancer stem cells have now been identified in numerous cancer types.  However, the drugs targeting the control of the genetic mechanism of the cancer stem cells are just now about to pay off for investors in the right stocks.  We believe that cancer's Achilles heel is finally in the crosshairs and that selecting the right investments in this relatively unappreciated area will provide explosive returns to investors.

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