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

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Why medical community still doubts herbal remedies

English: Herbal remedies for sale in San Juan ...

English: Herbal remedies for sale in San Juan de los Lagos, Mexico (Photo credit: Wikipedia)

We have all heard it:  herbal remedies can’t be wrong, they have been used for thousands of years.  In fact, it’s true…many cultures, tribes, medicine men, etc. have been using and in essence prescribing natural plant based herbal remedies for many many years….in fact, much longer than that of modern medicine/pharmaceuticals.
So why then is the medical community reluctant to embrace herbal medicines and remedies.  Although it’s fun to poke fun of doctors, medical administrators, insurance companies, and pharmaceutical executives, the universal distrust in these types of remedies is not unfounded.  Here is a small list of reasons: 1) Many herbal remedies were found to have good affects on one particular ailment (such as stomach discomfort) and then prescribed and suggested to work in other organ system (the liver, lungs, etc.) with little or no evidence.  2) Many herbal remedies have been linked to visual cues in how they were assigned to work.  For example, it is common to find that red fruits or seed products are often given to women for bleeding conditions as blood is red and so is the remedy.  3) Many herbal remedies over the years are assigned to work on various parts of the bodies as they were harvested in certain ways- functional links.  For example, the Cantonese believe that eating pig brain will make you smart, or if you have impotency- eating of dried and ground up ox testicles will help.  Although these are not plant remedies, these types of functional or anatomical links have dominated traditional remedies.  4) The vast majority of remedies, even though many have commonalities from independent groups around the world and have been used by millions, have no properly controlled studies to show that they actually work. 5) They are prescribed and administered in widely varying fashion. The list goes on and on and these objections are fair.  That does not mean that herbal remedies don’t work, it just means we have a long way to go before modern practitioners will embrace them.

The last time that a medical compound was successfully derived from a plant and used in clinical medicine was in 1967.  That agent/drug was Taxol.  That was a long time ago?  For a while people just stopped looking for them.  However, many are now pursuing this newly popular science; namely plant medicinal chemistry with newer techniques.  Who knows, maybe one of our next blockbusters will come from a herb, plant or natural product.   It might not only save lives but also teach us identify the chemical component that works in the plant itself.

Vitamins that kill?

Ok…the title is a bit over the top I know, but new and some not so new evidence suggests that this supplement craze (most vitamins) that is ever so popular now may actually be damaging and not helpful. 

How so?  Well a number of studies have now linked the over consumption of vitamin A, C and E to the development of a number of cancers including lung cancer, bladder cancer, and prostrate cancer.  Statistical analysis also showed an increase risk in premature death is a cohort (a subset) of people such as post menopausal women.  

It seems as if the antioxidant observations in aging, first made in the 1950’s, with natural antioxidants found in fruits and vegetables has now grown into a multibillion dollar industry with man made vitamins in the form of pills.  It is now clear with more and more studies using correct scientific and clinical methodology, that ingesting large (or even moderate) amounts of these supplements not only do NOT prevent illness as prescribed, but result in increased mortality, increased risk of certain cancers, and in some cases increase risk for heart complication.  This is scary folks. This is dangerous folks.

So, what to do?  First and foremost, something that we all know but for some reason refuse to practice (many of us); eat healthy fruits and vegetables that provide you with all the vitamins, minerals, fibers, etc. that your body needs and in the correct natural form.  Avoid taking supplements unless instructed to do so by your doctor (e.g. a pregnant women taking folic acid is absolutely advisable).  Especially steer away from those vitamins which are in far excess of the recommended daily doses (e.g the USDA has recommended dosages).  Extra vitamins do not mean extra protection.  Furthermore, if you are a vegetarian or on a strict dietary regime (or do not eat fruits, vegetables, and nuts) than you might need to take some supplement (but look for those at lower doses).

  Remember, antioxidants can be found in many forms…coffee, teas, vitamins, fruits, vegetables.  However, we now know that oxidants are natural and helpful as well.  Our own body produced them to fight infection and kill microorganisms.  So, oxidants and antioxidants are both important.  Let’s not get carried away bu sales adds and such and buy buy buy, based on what marketing executives tell us.

 

Cheers

Dr. C

Cancer info…watch what you read!

"seeds" used for brachytherapy of pr...

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Hello again.  Today I want to mention a few things about information that you will encounter on weekly basis in news, blogs, TV and such.

The first piece of advice (coming from a long time cancer researcher) is to simply be careful with the information you read.  Unless you are trained in the area of cancer, or statistics, or sometimes even psychology; it if often very hard to tell if the authors are being truthful or not.  Even if they are for real, it is very difficult to tell if the conclusions they make from their statements are true.  For example, people who love to drink coffee will look at the recent studies which show a positive impact on coffee drinking and prostate cancer and they will state that the studies now prove that all men should drink lots of coffee to avoid prostate cancer. If you don’t read the original information (and how many of us go back tot he original source these days)  and rely simply on the one blog you read, you may miss out on the fact that this study is an association study.  That means that there is no proof at all, only a link between those who drank lots of coffee or ten to twenty years and the risk of one kind of cancer.  You wont know that for women and breast cancer the studies are not the same as for men and prostate cancer.  So, read lots of stuff and stay informed, but read things carefully and with a grain of salt.

As you start to read more and more you will find that you can spot more and more errors or exaggerations more easily.  It comes only after you have started to see themes repeated over and over.  Then and only then can you start to pick up on how some folks will mold the truth around something they feel strongly in and hide certain details that will detract from their biases.  We all have biases one way or the other and that is OK, but the reader must understand this and should over time read things (about cancer in this case) from people on both sides of the same issue if possible.

What kind of blogs and information web sites are there and which ones should you be more careful about.

1.  The information only website.  The NIH and other cancer information promoting websites are usually going to be pretty good and trustworthy.  These wont bias you so much in one way or the other, but they will usually steer you away from alternative forms of therapy or avoid other issues that have less scientific validity.  There is nothing wrong with that and you just need to go see other websites if you want to learn more about those other area.  Many of these (like mine at Cancer Made Simple) will have trained scientists on their staff.

2.  Blog from people who had or have cancer.  These are a great source of information from people who have been there and done that.  These can be very fun to read and full of interesting information.  They are very useful for people who have the same or similar type of cancer that the blogger had or taking care of someone with that condition.  They, however can be subject to a lot of bias and it all depends on the prior experiences and disposition of the blogger him or herself.  Either way, they make great reading and tend to be less scientific but more day-to-day experiential.

3.  Blog or websites from retailers- be most careful with these (even with large companies).  Larger companies that have drugs or agents that are FDA approved and based on years of very good clinical data are of course more trustworthy that those who don’t have that.  However, companies are very VERY good and making their data look good and have huge budgets for marketing their products (of course legally) but often can mislead us.  However , the biggest problem out there lies in these very small companies or have no or little direct clinical data on cancer treatment, but who still try to sell you an anti-cancer therapy, drug, or agent anyway.  There are so many of those out there.  If the agent is perfectly safe, pure and clean, non toxic, and not too expensive, then it might not be a problem even if it is not effective.  If the product, is harmful (e.g. they ask you to take too much and it damages your liver), has undeclared chemical gents inside (e.g. melamine in milk from China), is very expensive for sugar-water, or is 100% useless (has no value at all), then it should not be consumed.  However, you won’t be able to tell so much.  You will know if they have done the proper studies and they will tell you and most of all show you by directing you to the published data.  Most don’t have it and never will.  Much out there is pure crap.  So, read these sites as they will talk about cancer and push you towards buying their products.  But, their information will be very biased….so use caution.

TV can also be highly misleading so ignore as many of the adds as possible as marketing is always greater than truth.  The news is a great source of information but when the anchorman or woman makes judgement about cancer related information- ignore these.  They have no clue and are just adding their own two cents and can often be way off the mark.

There are many other kinds of websites and blogs relating to cancer.  So read and learn as much as you can!  Just use caution.

Thank you….Dr C  Cancer Made Simple

Melanoma: its only skin deep or is it?

Skin Cancer: Recognition and Management

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Skin cancer is actually quite nicely treatable despite the horror stories you might hear.  But, here is the catch….only when it is caught early.  Melanoma (the lethal form of skin cancer) before it spreads is fairly easy to treat…scary but treatable.  Unfortunately, as is the case with many cancers, once it has spread to different sites of your body, in a process called metastasis, it is very difficult to treat.  The most severe stage of the disease is known as stage IV metastatic melanoma, and this is a deadly incurable form of the disease.  Sadly, the only approved drug, a type of chemotherapy, only reduced the cancer in 10% of patients.  What’s even worse is that even in those 10% where the drug seems to work, the patients will still die of the disease.  This drug, like many, poison the cell as it undergoes cell division in a process known as proliferation.  To make a long story short, any dividing cell is potentially vulnerable to this drug so it is a very broad killer of cells.  The melanoma cells are slightly more sensitive to this drug, but so are hair follicles, cells lining the gut, and other rapidly dividing cells in your body. 

As is the case for many forms of cancer, researchers are looking for agents that might be a little bit (or a whole lot) more selective in targeting the cancer cell itself and sparing the normal cells (like the hair follicles, etc.).  Melanoma is one cancer that has been probably the most studied in this area.  One such area of investigation is the use of ‘immunotherapy’ to try to treat the disease.  In these types of therapies certain drugs or proteins are used to help the patients’ own immune system to defend against the cancer.  One of these developed drugs is an antibody known as ipilimumab or anti-CTLA4.  This antibody binds CTLA4 that is present on the T cell in hopes of increasing the anti-T cell function against the cancer.  It does seem to work in some patients who receive this in addition to another agent.  This other agent is a protein that is found highly expressed on the cancer cells itself known as gp100.  This protein is given as a vaccine to help boost the T cell response against the cancer.  These two together do show some promise in some patients who have stage IV melanoma.  However, at the moment the final clinical trials are being conducted, so it is not widely available and not proven yet. 

Other companies are developing drugs that interfere with signaling pathways that are highly activated in cancer cells and less so in on cancer cells.  50% of all patients with advanced melanoma are known to have mutations in a pathway that leads to activated growth.  The mutations map to a protein (enzyme) known as BRAF.  This mutation keeps the enzyme protein in the active state that leads to continued growth where in normal cells the protein is keep in an inactive state.  Chemical drugs have been found that bind to a certain region in the protein that blocks this mutated protein and thus helps to either kill the cell expressing the mutated protein BRAF or at least stop it from being active.  Again, this novel drug is still undergoing testing in clinical trials and if it passes muster it will be released for use in cancer centers. 

Limitations:  There are certainly going to be some limitation that make these and probably most future therapies less effective that we wish.  One has to do with cost.  Immunotherapies tend to be very expensive.  The antibodies or proteins cost a lot to make and the patient ends up paying tens of thousands of dollars per year (sometimes more).  The novel chemical drugs are usually more expensive than existing drugs as the drug company passes off the cost of development to the consumer (the cancer patient).  The other issue is that even with these new ‘cancer specific’ drugs, different patients will react differently.  It is VERY hard to predict which patients will respond well or not.  For the BRAF inhibitor discussed above, it is fairly easy to determine which patients to give the drug to (the 50% of the patients who have the mutation and not that ones that do not have mutated forms of BRAF).  But, it is another thing to know which patients will respond and which will not.  The same goes for the immunotherapies.  No one can predict which patients will response to immunotherapies…we just don’t know enough about the millions of different things that happen in human bodies that can interfere with a good anti-cancer immune response. 

So, lest you get too depressed and think that no one is doing anything about it…millions of dollars and some of the world’s brightest scientist and clinicians are working to solve this problem of the lethality of late stage skin cancer.  But, it takes time and it is complex.

Thankyou for reading and do let me know if you have any further questions/comments about advanced forms of skin cancer or cancer in general.  Be sure to visit my cancer information website at Cancer Made Simple!

Dr. C 

Cancer Information Made Easy

Correlation between smoking and lung cancer in...

Image via Wikipedia

 

I am back after a brief hiatus.  I had some troubles with my blog and I think i have fixed it.  Please do read about the various topics covering all sorts of areas around cancer and do leave me comments and suggestions with further areas you would like to see added/discussed.

Thanks for looking and my newly redesigned web site that relates to this content.  Cancer Made Simple

Cure

This figure shows the heterogeneity of cancer ...

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So, what do you think a cure means to you?  It probably means something like…not having cancer for the rest of your life after a particular treatment…or something like that?  Is that right?  Isn’t that what a patient who has cancer might think if he/she was talking about a cure?  Well, unfortunately this is not the case in medical terms and what scientific publications mean when they talk about cure.  When clinical folks talk about cures…they are referring to the ability of a certain treatment to extend the life of a patient without any symptoms of the disease for five years.  Not for life!  Thus, progression free survival for five years defines a cure.  Why do I bring this up?  It is because a patient should know this when they talk to an oncolgist or read scientific literature and not assume that a cure means for life.  Actually, what we in the medical community should do is replace the word ‘cure’ with something else.  We should not use that term if we don’t mean what people on the street mean.  I think many in the media are also not aware and thus, they report on cure for this and that without really being accurate in any way.  So, please be careful about using the word cure…please don’t allow expectations to be too great in terms of cures for most cancers.  We are working on it but we are not there yet!