Can HIV be used as therapy for cancer?

Diagram of the HIV virus.

Diagram of the HIV virus. (Photo credit: Wikipedia)

Every so often, a report comes out in the news that grabs our attention.  Here is one of them.  The virus responsible for AIDS, a deadly disease with no real cure, has been successfully used to treat a few people with certain types of cancer.  Now wait a minute, you mean we are giving someone HIV?  Are we replacing one fatal disease (viral) for another fatal disease (cancer)?  No and no. Let me explain.

Human viruses that cause disease have successfully evolved to infect and survive in human tissues and cells.  HIV has evolved so well that it infects humans cells and avoids immune elimination and of course eventually causes death.  Other viruses are also very effective at infecting human cells and surviving to the extent that they replicate (or divide) very well in the body.  Viruses, although extremely simple in their makeup, have also evolved clever ways to manipulate the human cell’s own machinery for itself.  One of the things that the HIV viruses does very well is to integrate it’s genetic material into the human cells.  So, why not modify the virus so that it no longer kills you (we call this removing the virulent properties) but still has all the infective, survival and genetic integration properties. This is exactly what is being done.

For many years, a virus known as adenovirus has been modified to remove it’s harmful properties and keep it’s infective and replication processes.  This has been done rather successfully, but using these ‘modified viruses’ has proven rather difficult…do to a host of reasons.  What is new now is that the HIV virus was used as a viral vector in this case.  Thus, the properties that allow HIV to kill humans were removed, but the properties that allow HIV to infect human cells and integrate their genetic elements were kept.  It is perhaps not surprising that after nearly 15 years of HIV research and trillions of dollars being spent, we have now reached a stage where we know enough about the virus to start modifying it for use as therapy.

OK, so how is it being used.  Let’s first look at the cancer in question.  Leukemia is a cancer of the blood…often it is a cancer of the B cells specifically.  These B cells, instead of protecting you from pathogens by making B cells and then dying like normal cells, become transformed and keep dividing uncontrollably.  Mutations in the genome of the B cells result in a cancer of these cells that grows to such a large extent that they start preventing the normal function of the blood and the immune system.  These cancerous B cells start to overtake the body.  Getting rid of them permanently is difficult as bone marrow transplants are the best way to permanently remove them.  However, this can only be done with individuals who are healthy, and who have their cancer in remission (one must have a good heart, have a functioning normal immune system, etc.). BM transplants are still high risk and have many side effects and are very expensive, but can be life saving.  Not everyone can qualify for this procedure.  Chemotherapy often fails but is used to try and control the disease, but often as a temporary measure for many leukemias.  So, other therapies are often needed.

Using a modified and non lethal form of the HIV virus that infects T cell, scientists mixed a these cells.  However, the HIV itself was engineered to express a modified protein that allows the T cells to recognize the B cell, and then to kill it.  So, a mix of this genetically engineered HIV was allowed to infect the patients own T cells and those T cells are now able to recognize and destroy the B cells in the patient.  Confusing…yes, but don’t worry too much about the details.  In general HIV plus the patients own T cells were used to allow the T cells to kill the cancer cells.

Sounds sexy sure.  However a few things to recognize before getting too ahead of ourselves.  1) All B cells are killed not only the cancerous B cells and thus treatment makes you VERY sick as your immune system is shot for quite some time after the procedure (but this is only temporary as your immune system will recover but the cancer wont).  2) This may not work on everyone and only a small amount of people have been tested.  3) This is an example of personalized medicine and is very costly.  4) It may be years, if ever, before the FDA recognizes and approves of this type of therapy.  5) No one knows the potential dangers if any with using HIV as an infection tool.

So, interesting…let’s hope they can expand their trial and show long term studies that ‘prove’ that this works.  But for now, its a small step in the right direction!!!

 

Thank you

Dr C

Hallmarks of cancer

English: Cancer cells photographed by camera a...

English: Cancer cells photographed by camera attached to microscope in time-lapse manner. (Photo credit: Wikipedia)

II was inspired to add another blog today after a friend/former colleague of mine came in to see me and mentioned he had been reading my blog (thanks Allan).  So, today I have decided to embark on describing the hallmarks of cancer as we now understand them (hopefully using simple words and concepts as some of this does get kinda’ murky).

In 2000, a well known cancer scientists named R. Weinberg and his colleague published a review of the major hallmarks of all cancer cells (and thus of cancer itself).  In that original publication, he described six hallmarks, that was an increase in the previously established two.  There are now about eight that are widely accepted.  So, let’s start with the original two.

We all have normal tissues and cells in our body and many of the cells turnover relatively frequently.  Cellular turnover refers tot he process of dying and dividing cells.  Thus, new cells are made from dividing older cells and other old cells die off.  As the new cells are made, some of them may acquire new mutations.  Some of the cells may also have old mutations or may even harbor mutations that were inherited.  If these mutations affect the survival of the cells than we call them oncogenes (#1 hallmark).  If these mutations prevent the killing (or what is known as apoptosis, or programmed cell death) then the cells don’t die when they are supposed to (the #2 hallmark of cancer).  We have known for many years that all cancer cells derive from cells that keep growing and that don’t die.

Later, we started to appreciate that there were some other characteristics that we could ascribe to all cancer cells in addition to these two.  Instead of needing to turn on and off growth signals like normal cells, cancer cells are self sufficient in growth signals.  That means that the signals that make the cells grow, don’t turn off.  As long as their is cellular energy, then the cells keeps going.  That is hallmark #3.  Another attribute that all cancer cells have is that they are actually insensitive to growth signals, this is in addition to the fact they they evade death signals.  So, the signals that they receive from death inducing agents are either ignored or fuel growth or expansion. That is the 4th hallmark.  Two additional changes occur that are universal to all cancers, but some early cancers may not progress o this state.  One of these is the promotion of sustained blood supply to the tumor and thus the cancer cell (supplying it with nutrients and oxygen, etc.).  This 5th hallmark is also known as angiogenisis.  Looking at cancers that have advanced it is clear that they have increased vascular supply than the surrounding tissues.  Finally, the 6th hallmark of cancer is that of tissue invasion.  Aggressive cancers and the cells that make them up typically run out of food supply and become more aggressive and seek out new areas of the body.  In order to do so they need to secret products that help them ‘digest’ their environment and all of the fibrotic material that accumulates.  This 6th hallmark of cancer is also referred to as metastasis.  The cancer is usually more aggressive and serious once it has moved onto and latches onto its new location.  It is also much harder to treat.

Two newly recognized and agreed upon processes occur in cancers as well (and thus the cells that make them up).  The 7th hallmark of cancer is the ability of the cancer cells to escape the immune response.  Normally, the immune response would look at mutated proteins (that are found in most cancer cells) and try to destroy them.  However, cancer cells evolve many unique ways to evade immune destruction and recognition.  Finally, the 8th hallmark of cancer cells is something called metabolic reprogramming.  This basically means that the metabolism of the cells itself no longer mirror what the normal cell has.  The genes, energy usage, and most metabolic processes have permanently changes into a more aggressive, energy hungry pro-growth state.

Thus, as you can see, cancer is not so simple.  The cells that make up the cancer have changed in so many ways.  This is partially why it is so hard to eliminate cancer once it has taken hold.  There are quite a number of pathways involved in all 8 of these processes.  Since the early 80’s we have really learned a lot about cancer; certainly we have learned how complicated they are.  We have developed drugs against every single one of these 8 hallmarks, but we have not been able to cure most cancers and permanently eliminate many tumors (especially of caught late).

Thank you for reading and i do hope that is made cancer a bit more easy to understand.
Do visit www.cancermadesimple.com for more information.

Dr. C

Cancer prognosis and statistics

Cancer A~

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As I have mentioned before, cancer has a lot to do with number.  Risk, prognosis, and so on are rooted in some simple types of math.  Statistics are often thought of as cold unfeeling facts that do not help much.  The first part may be true but the last part is far from truth.  However, psychology is very important when people talk about cancer with one another.  statistics (if the numbers are good) help to overcome issues related to bias and personal feeling about things so that we can get a better handle on certain issues related to cancer.  Many of us (if not all) fall into recognizable patterns often; how many times have we heard someone tell us, my friend or relative was cured of this or that.  Most likely we remember that fact and rely on that treatment issue without much thought.  We may even rely on one persons recommendation to take a certain supplement because they swear how he/she has overcome some serious complications etc.  It’s natrual to think like this, but it’s also a bit destructive.  The ‘n’ of one is not a powerful statistic at all.  Anecdotal evidence…many people have told me this or that, is also easy to rely on.  What we miss in the ‘n’ of one or the anecdotal evidence is the others who took the same drug/supplement that had no benefits.  Or we fail to realize that the person who is telling us the evidence is biased or perhaps not accurate at all.  This is often the case for most folks who are promoting self-help, alternative medicines, or supplements…that all too often have little evidence for being effective. 

So what do we do about all of this….well think.  Ask yourself about the evidence before you start buying expensive supplements.  If the person selling you the stuff or your relative who believes in some remedy for the common cold…please ask them to produce some rational evidence to you. 

So what is prognosis?  It is a guess that doctors give that is often based on statistics from a large or even small group of patients who have had the same conditions as you.  More specifically, for cancer patients it is the prediction of the future course and outcome of a cancer and an indication of the likelihood of recovery from that cancer.  So, from this you might guess a few things.  A prognosis is not fact…it’s an educated guess.  A prognosis (an estimate for example of how long you have to live with a particular treatment for example) is limited by the ‘power’ of the number of individuals who have been previously analyzed.  So, if it’s the common forms of breast cancer the prognosis might be really accurate as there is a huge patient number that allow for very good statistical interpretation.  If it’s mesothelioma, a much more rare cancer, the prognostication might not be very accurate.  Furthermore, no two people are alike…our immune systems are different, are genetics are different, and out habits (such as eating, etc.) and thus we might not respond at all like the average patient.  So, a given prognosis is an estimate…but not final or finite.  It is a rough guideline.  Put it this way, if good statistical information is available…why not put some faith in it and listen to the doctor who gives you an estimate about your response?  If the statistical information is weak or based on one person’s advice or anecdotal evidence, why not questions the information and rely less on it?  Keep an open mind but don’t ignore previously recorded evidence.  A good prognosis will boost your confidence and have a positive impact on your thinking and a negative/poor prognosis will sap your confidence and perhaps may even have a negative impact on your health. 

This leads me to my final comment…statistics can be cold numbers that don’t reveal everything.  If the doctor gives you a poor prognostic for your survival with cancer X, you may wish to ask him what he uses for evidence.  How large is the sample size or the trial size that he is using?  He will know that information or can find it fairly quickly.  Do not give up just because you have been told your prognosis is poor.  The evidence behind that prognosis is poor and you may respond differently (the mean may not tell the whole story).  Ask more questions the more negative the news is…you owe it to yourself!!

Ok, I think I will stop now…please do ask me to clarify anything if you wish!  Thanks for reading.  Do look at cancer made simple for more information!!! 

Dr. C

The war on cancer: 3 challenges

Cell phone tower cleverly disguised to look li...

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This blog report is based on Dr. Mukherjee’s NY Times commentary made on July 16th.  To summarize his observations, cancer prevention faces an uphill battle due to three major forces; science, politics and society.

To explain this he brings up the highly contentious issue of cell phone usage and it’s link to cancer.  Scientifically, there is little proof that electromagnetic radiation that is emitted from active connections from cell phones lead to increased incidences in cancer.  The type of radiation that is emitted is so weak that it has never been shown in any experiments of any kind to damage DNA (a fundamental hallmark of cancer development).  However, an interphone study that was conducted that asked people to state their cell phone usage patients (low, medium or high) and then followed them for a period of time to look for cancer occurrence (brain cancer), found a link.  Other studies have since found that what people perceive as their phone usage is frequently very different from reality (that is of their actual usage).  So, this study is probably not very accurate.  Furthermore, it is easy to ask what the incidence of cancer was before the adoption of cell phone and after.  When one does that there is NO correlation at all to phone usage and cancer incidence.  However, this has not stopped the WHO to place cell phone usage in the ‘possible carcinogen’ category.  This may not be a mistake itself, but reminds us that despite science policy and warnings will still be made. 

Another issue that focused on politics was focused on formaldehyde.  This example is the exact polar opposite of the above one.  Here, it is well established that formaldehyde in the laboratory caused DNA damage that leads to cancer.  Furthermore, those who work in the formaldehyde industry do develop certain cancers at higher incidences (at least certain kinds of blood cancers).  These studies occurred over 30 years ago and only now did the National Toxicology Program only now issued a statement calling this chemical a carcinogen.  The large reason behind this was that science was finally placed before politics.  Lobbying efforts by companies who make the chemical have fought long and hard to stop any major governmental organizations from labelling this chemical as such.  They, of course would prefer if nothing negative is ever said about any of their many chemical/compounds/etc that make them billions of dollars.  I would bet my money on the fact that most if not all of the senior lobbyist and CEO’s of these chemical companies that make formaldehyde have not worked with the raw processing of this drug and certainly don’t suffer from the carcinogenic events (if they or their families did, I assume they might not put profits before safety). 

Finally, despite strong evidence from the 50’s onward, tobacco companies have been doing everything they possibly can to prevent any rules that are passed that might negatively impact sales.  Historic and unprecedented/massive lawsuits against the major tobacco companies did curtail the sales of cigarettes for some time but they seem to have been on the rise again.  Australia has just enacted some of the toughest laws on cigarette packaging in the world.  The US has just adopted some strict guidelines that require that graphic consequences of cigarette smoking be shown on the cartons despite huge resistance by the industry.  It has been shown that plain packaging and ‘gross imaging’ might just dissuade non smokers to avoid the habit causing agents.  The cost to health and healthcare is too great to ignore and the link of smoking to cancer is too great to ignore! 

This summarizes what was written.  Science should triumph over lobbying efforts to reveal truth to Americans (and to those living in all countries), politics should not be allowed to dominate over policies regulation safety, and social norms (such as smoking) should be kep in check by aggressive policies to assist people avoid bad habits. 

 Thanks….Dr. C Cancer Made Simple!

Old drugs get a new lease on life: cancer!

Age-standardised death rates from Breast cance...

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When drug companies make new drugs they often spend million and millions of dollars on them.  Due to regulatory issues, new drugs can only be used for one very specific purpose (that at which is was designed and tested for).  However, if the drug is included in the treatment cycle and FDA approved it can ear a company billions of dollars in income.  As you might imagine the incentive to discover new areas of treatment for the new drug is huge.  This is not a bad thing.  There are conditions here one’s immune system is too active and needs to be suppressed.  For example, for transplantation where a donors organ or blood is put into a patient, large amounts of immunosuppressant drugs are used.  These drugs often inhibit the growth or activation of immune cells in the patient.  It turns out that the very same pathways that some of these drugs work in blocking the immune system also work fairly well in blocking cancer cells.  This is where the link is now being pursued by many drug companies.  I will just bring up one example here below but in the future I will introduce other examples.

Recently, Novartis (a big pharmaceutical company) had good success with an immunosuppressant for Breast Cancer.  The drug Afinitor (R) is a type of drug known as Everolimus which was originally designed to block a protein pathway in the cell known as MTOR.  This pathway if blocked prevents activation and proliferation of T cells and is thus acts to prevent immune responses.  Over the years it has also been approved by the FDA to be used to treat late stage kidney cancer, certain metastatic pancreatic cancers and a few other conditions. 

Recently, ver strong clinical data has encouraged the maker of Afinitor (R), Novartis to file for worldwide approval for the use of this mTOR inhibitor in breast cancer patients.  Phase III clinical trials with 700 patients have shown that patients who took this drug plus a hormone inhibitor in advanced breast cancer settings had delayed tumor growth in comparison to estrogen inhibitor therapy alone.  This combination of the two drugs allowed patients who had breast cancer delay their treatment with chemotherapy and slows down the hormone resistance that develops after a time in many of these women.  If awarded, this drug will make over a billion dollars for Novartis. 

So, this is just one example of re-use of a drug that had once been used only for inhibiting the immune system and now used in breast cancer.  It’s an example of an old drug with a new target.    

Thanks …Dr C

Cancer Made Simple

2011 Cancer Stats

Correlation between smoking and lung cancer in...

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Just a quick update for you stats junkies on the status of cancer deaths and incidences for 2011. 

The estimated number of Americans (sorry the US has some of the best stats out there and is upfront about publishing those numbers) living with cancer today in 2001 is about 11.7 million.  This number is actually a bit misleading as it estimates the total number of people who had cancer (either currently or previously in 2007).  Some of these folks have died of cancer, dies of other causes, or are still alive today (with or without cancer).  However, the number of new cancer cases for 2011 is estimated to be about 1.6 million people.  Thus, cancer deaths and new cancer cases have away of balancing each other out (not always evenly).  About 572,000 people are expected to die of cancer this year. 

Men have about a 1 in 2 lifetime risk in developing cancer while women have about a 1 and 3 chance.  Much of that has to do with cancer from smoking which up until the 80’2 was mostly a problem for men.  In fact, in 2011 cancer related complications from smoking is estimated to kill about 171,600 people.  This is sad as this type of cancer is preventable.  This will change as the women who started smoking in large numbers after men (late 70’2 and further) will soon start to see the delayed increase in lung cancer rates. 

Other preventable cancers (related to obesity, poor nutrition, and infectious agents such as HPV) will result in about 572,000 deaths. It is sad as many of these can be prevented by improving diets, exercising, and lifestyle changes such as smoking cessation and reduced alcohol consumption (easier said than done).  2 million skin cancers are detected annually and many of these can be prevented by appropriate skin care products or a reduction in prolonged exposure.  Many of these cancers are not lethal (if they are detected early the success rate of survival is high) but costs add to ever-increasing health care  burdens. 

Today, heart disease is the biggest killer of Americans…this is followed by cancer deaths at number two.  Today, one in four Americans can be expected to die of cancer.  The typical age of developing cancer is about 55 (in fact, 78% of all cancers are detected at that age or older).

However, as cancer becomes more frequent it is important to ask what is our overall survival rates for those with cancer on average.  The most up to date 5 year survival rates for people with cancer (all forms of cancer combined) is about 68%.  That has improved from a previous rate of about 50%.  However, it is important to note that these numbers are very different from one cancer to another.  As we catch cancer earlier we are able to treat it better.  As treatments improve for some cancers, people are able to survive longer. 

The top ten cancer killers are Lung, Prostate, Colon, Pancreas, Liver, leukemia, esophagus, Bladder, Lymphoma, and Kidney (in men).  In women the second cancer killer is breast instead of Prostate and Ovary, Uterine, and Brain cancers appear on the top ten list. 

Anyhow, I will stop at this and recommend that you read the Cancer Facts and Figures 20011 from the American Cancer Society which is available online.

Thanks, Dr. C

Cancer made Simple

Drug companies and cancer

The graph shows the annual number of cases of ...

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So….where are we now with new therapies that are actually saving lives for people with cancer?  As I have discussed before, have we seen any progress in the last ten years?  We have certainly advanced our knowledge of cancer and signaling pathways and have even come up with new strategies to target cancer.  Let me make a quick list of the things we have learned in the last ten to 15 years…

1.  We have now started looking for mutations in patients with certain kinds of cancer such as advanced melanoma (BRAF mutation V600E) as a means of identifying patients who should respond favorably to drugs that target those mutations.

2. Immunotherapy has potential to work (and does so in rare cases) but still not well against some cancers.   Antibody therapy is used against some cancers such as B cell cancer and even now in skin cancer with some success.  Things that help boost the immune system do show limited efficacy in some cancers. 

3.  Drug companies have developed some interesting other types of therapies that rely on dendritic cell vaccines and a few others.  A vaccine is a bit different from antibodies in that they are material that you can use that comes from the cancer cell itself or from a newly designed product (e.g. human dendritic cells given bits of tumor antigens) to patients to help them boost their anti cancer immunity.  These have limited effects and only work with certain patients and we can’t always anticipate who will benefit and who won’t.  Other approaches include the use of cancer RNA, DNA, cytokine stimulated dendritic cells, etc.  Only one drug in this class has been approved by the FDA so far and that is against very advanced protate cancer.

4. Small peptides (proteins) and other small molecules are being developed now that target various newly discovered cancer specific pathways (again we have learned a great deal about pathways in cancer that don’t exist in normal cells).  In melanoma (skin cancer) about 45 different cancer specific peptides have been identified (ones that the immune system recognizes and trials or pre clinical research is being conducted with many of them). 

5.  We have learned that treating cancers with drugs that target specific mutations (a classic example is Gleevec(R) that targets the BCR:ABL protein in a cancer called CML) have the potential of driving the cancer to become resistant to that drug (via further mutations).  This is somewhat similar to the anti-viral therapy for AIDS (HIV-1 disease).

  6.  We can sub-classify cancer better and stage it better.  It is not clear that this helps with treatment, but it certainly helps to give the patient individualized prognosis (e.g. give them with more accuracy his/her life expectancy with a cancer at a specific stage).  In some cases it does help to prolong life.

7.  Some drugs on the market can now be analyzed for long-term efficacies.  For example, for some drugs that have been used for 10 years or more for the same patient (same cancer) we can come up with better 10 year survival rates, etc.  This, of course, can be done on patients who were treated with a cancer therapy (even immunotherapy) ten years ago, even if the drug was stopped.  We can and have gotten better numbers now at longer term survival (perhaps in the future cure rates will be measured at longer time points than 5 years).

8.  Viral vaccines against papilloma virus for teens (females only) is going to revolutionize the HPV associated cancers.  These vaccines (initiated in many countries now) are going to reduce significantly the risk of getting certain cancer in women…the biggest of which is cervical cancer.  It will be interesting to see if the same can be done in the future for other viral associated cancers such as liver cancer (HCV or HBV), stomach cancer, and a few others (e.g. EBV and NPC). 

Anyhow, there is much we have learned (and this was not comprehensive).  However, it is not clear that we are truly extending the lives of many patients with cancer (better than we were ten years ago).  It seems that for advanced cancer patients we are in the same position as we were years ago.  Certainly for newly diagnosed cancers such as prostate cancer, we can do more now than ever to get most patients to continue to live cancer free lives.  We have a long way to go…we have got to find treatments that work for patients with cancers that have metastasized for example.  We have got to figure out how to keep costs low.  We have got to figure out how to do better screening or if screening is really necessary. Other avenues that are gaining interest are treatment that do not rely on “western medical” interventions.  This area will continue to grow.

Thanks for reading….please leave me comments!

Cancer made simple!