Posted on 01/04/2014 8:08:25 PM PST by SeekAndFind
“THERE is no treatment.” This is the conclusion of an Egyptian papyrus, written around 3000BC, that is the oldest known description of the scourge that is now called “cancer”. And so, more or less, it remained until the 20th century, for merely excising a tumour by surgery rarely eliminates it. Only when doctors worked out how to back up the surgeon’s knife with drugs and radiation did cancer begin to succumb to treatment—albeit, to start with, in a pretty crude fashion.
Now, however, that crudeness is rapidly giving way to sophistication, as a new wave of cancer treatments comes to market. In 2012 more than 500 potential cancer drugs were under investigation, according to a survey by IMS Health, an American research group—over five times as many as were being developed in the next biggest category, diabetes.
Three trends are helping to fill this cancer-drug cornucopia. One is the increase in demand as people live longer, and thus become more likely to develop cancer. According to the World Health Organisation, there were 14m new cases of cancer around the world in 2012. In 2030 there will be nearly 22m. The second trend is the rising price of cancer drugs, particularly in America, the biggest market. More expensive drugs increase profitability. The third is a rapid expansion of scientific knowledge about cancer, the result of both the plummeting cost of genetic sequencing (see chart) and a better understanding of how to recruit the immune system to attack the disease.
Or, rather, the diseases. For there are hundreds of kinds of cancer. Their common factor is that they are all caused by cells dividing interminably because something has gone wrong with the victim’s genes. The problem may be extra copies of a crucial gene, damage to a gene, modifications that affect a gene’s function, or the merger of two chromosomes to create a novel gene not seen in healthy cells. Sometimes these problems are inherited. More often they arise when cellular wear and tear goes unrepaired, a process exacerbated by certain chemicals and radiation.
Understanding the genetic changes that cause particular cancers may suggest ways to attack them with specially tailored drugs. The first example of such a targeted treatment came in 2001, when Novartis launched Gleevec, a treatment for chronic myeloid leukaemia. Gleevec blocks the activity of a protein called BCR-ABL, which is the product of an abnormal gene created by a merger of chromosomes 9 and 22. Before Gleevec, less than a third of those diagnosed with chronic myeloid leukaemia were still alive five years later. After it became available, that figure jumped to 90%.
New magic bullets Gleevec’s success inspired others to search for targeted cancer drugs. For example, Pfizer came up with crizotinib (sold under the brand name Xalcori), for lung-cancer patients with a mutated version of a gene called ALK, which encodes a protein that instructs lung cells to divide uncontrollably. And Roche developed vemurafenib (sold as Zelboraf), which goes after another rogue protein, generated by a mutated version of a gene called BRAF. It tells skin cells to reproduce, causing melanoma.
Though much better than older cancer drugs, Gleevec and its successors are not perfect. Many cancers are driven by more than one mutation. Cells also tend to pick up new mutations as they divide. Cancer cells divide a lot, so mutations can accumulate rapidly. And sometimes, to add to the problem, one of the enabling mutations of a cancer is of a gene involved in the DNA-repair mechanism, which a healthy cell would use to deal with mutations. BRCA1 and BRCA2, both often implicated in breast cancer, are DNA-repair genes.
DNA sequencing means it is becoming possible to track mutations, one tumour at a time. This helps in understanding how cancers in different tissues work and it also holds out the hope of treatments tailored even more closely to an individual’s needs.
The International Cancer Genome Consortium (ICGC), is doing this for 50 different sorts of cancer, with a global team studying the genomes of more than 25,000 individual tumours. Researchers working on the Cancer Genome Atlas, an American effort that is part of the ICGC, published a series of papers in 2013 showing some of the complex relationships. Chris Sander of Memorial Sloan-Kettering Cancer Centre, in New York, used an algorithm based on tumours’ genetic and epigenetic characteristics to describe 31 subclasses of cancer. Tumours from one type of lung cancer, for example, share traits with those of head and neck cancer. Li Ding, of Washington University, in St Louis, examined more than 3,000 tumours across 12 types of cancer. She reported 127 mutated genes that seem to propel cancer, with most tumours having between two and six mutations.
Dual roles Identifying common genes is only the start. Some mutations seem to play starring roles in one cancer while being supporting characters in another. For example, Dr Ding discovered that the BRAF mutation, known to be present in about half of melanomas, was also found in other cancers, such as 7% of lung adenocarcinomas and 4% of colon and rectal carcinomas.
Even though there remains more basic science to be explored, the genetic approach points to a new way of matching patients to drugs. At the moment, many targeted cancer drugs are accompanied by a diagnostic test for the relevant mutation. The falling cost of sequencing means that a patient might now be tested for hundreds of mutations or even his full “exome” (the DNA that encodes proteins, less than 2% of the total). This means that someone who became resistant to one treatment could immediately be given another, based on the results of such tests. He might even be given a cocktail of treatments in the way that a cocktail of antiretroviral drugs is used to suppress HIV.
Cheaper sequencing is also changing the way that clinical trials are conducted. In November a group of academic researchers and companies, in collaboration with America’s National Cancer Institute, announced the Master Protocol trial. This will examine five potential treatments for squamous-cell carcinoma, a type of lung cancer. Rather than hunting separately for five groups of patients with the mutations relevant to each drug, the researchers will use a test from Foundation Medicine, a company that screens patients for abnormalities in 236 genes linked to cancer. They will then match volunteers with each of the five drugs. This approach cuts the administrative time and hassle of what would otherwise be a huge undertaking.
The other novel approach to treating cancer is to rally the immune system to join the fight. Ipilimumab, a drug to treat melanoma, was launched in 2011 by Bristol-Myers Squibb, branded as Yervoy. It is a so-called “checkpoint inhibitor”, which by removing a blocking mechanism allows immune-system cells called T-lymphocytes to attack cancer cells (as they are pictured doing above). The results in some people have been remarkable, but not so in others.
Now other checkpoint inhibitors are being developed. Nivolumab, also from Bristol-Myers Squibb, MK-3475 from Merck, and MPDL3280A from Roche also unleash the immune system on cancer cells. These drugs, moreover, could be effective in more than one type of cancer. Ipilimumab may also fight lung cancer and prostate cancer. In June Roy Herbst, of Yale University, showed that MPDL3280A helped the immune system fight several different types of tumours.
Other medicines are at earlier stages of development. Bristol-Myers Squibb, for example, is testing a chemical that binds to interleukin-21 receptors on T-lymphocytes and other immune cells, helping the T-cells survive and boosting their activity. Unlike checkpoint inhibitors, which work by releasing the brakes on immune cells, this drug pushes the accelerator.
In the lab researchers are trying a variety of approaches. Luigi Naldini of the San Raffaele Telethon Institute for Gene Therapy, in Milan, and his colleagues report this week in Science Translational Medicine that they genetically modified stem cells to make white blood cells that produced a certain protein, interferon, that helped clear tumour cells in mice.
It may, indeed, be possible to combine the two approaches of targeted drugs and immunotherapy. Bristol-Myers Squibb has already tried this, testing ipilimumab in combination with Roche’s targeted melanoma treatment, vemurafenib. Researchers stopped the trial in April because of signs of liver toxicity, but that does not mean the general idea is unsound.
On December 5th, for example, GlaxoSmithKline announced partnerships with six academic research centres to develop new therapeutic drug combinations. Axel Hoos, the company’s vice-president for oncology, says the firm may soon test a targeted drug in combination with an immunotherapy from another company.
This approach could lead to prescribable treatments arriving faster if promising combinations are tested before either component had been approved for use by itself—a process recently made easier by a change in the rules by the Food and Drug Administration, America’s drug regulator.
Who is able to use these wonder drugs, if and when they become available, will depend on how deep are the pockets of those who are paying for them. In America a typical course of four doses of ipilimumab costs more than $100,000. Like all wars, the one against cancer is going to cost a lot of money, one way or another.
The cancer industry is much too big to fail.
I read once that researchers that made strides in curing cancer got their funding cut off. Big money in treating cancer.
Disagree. There is an enormous effort underway to find effective treatments. Unless the government completely screws up the health care system, in 15 years many tumor types will be managed successfully by drug therapy, similar to the way that CML or NHL are managed today.
I agree. A lot of members of the pharmaceutical industry have died of cancer. No one is hiding some secret cure.
I'm about as cynical as anyone can be, but I can't see the big "cancer conspiracy" as something real. The execs as the drug companies have watched their wives die of cancer, the researchers have children with leukemia, the corp. lawyers have mothers who died much too young. These people want the cure just as much as anyone else.
>>No one is hiding some secret cure.<<
That’s the one reason why I am such a firm believer in trying every ‘cure’ that has a decent history behind it. Many of the homeopathic cures have helped keep a lot of cancer patients alive for many more years than they otherwise would have lived. Just because a treatment plan doesn’t cost a lot of money is not to say it will be ineffective. Never quit fighting.
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I hope many blessings are bestowed upon all of you and your loved ones in 2014!
My regular MD told me of one of his patients who refused chemo. Why? I don’t know but the Doc told him to change his lifestyle. Exercise more , eat better. Cut out the stressful things in his life. Six months later the guys tumors had shrunk to 25% of their original size.
You mean it is going to cost a lot of money to win. Losing can be accomplished quite easily and inexpensively.
What will be the next thing for people to die from? As there become more medicines and treatments more people are brushing up against the maximum number of years our personal mental and physical factories can operate. Life expectancy has doubled since 1850 but maximum human life span hasn’t changed much in 3,000 years. In the future the aged will just fade away.
drug companies aren’t interested in curing cancer any more than the cancer charities are. of course people with cancer and their loved ones are used as cover for them, but they aren’t gong to cure a moneymaker for them.
most docs won’t do chemo. they would go the route of that patient, or resign themselves to die.
“In the future the aged will just fade away.”
That happens now. I have watched as patients in their 90’s were going along just fine and then they developed what I call “the Dwindles” and they died within a few months. The key sign is always that they can no longer stand on their own. Their relatives wanted me to tell them why and all I could come up with was “old age”. They human body just poops out eventually.
“I’m about as cynical as anyone can be, but I can’t see the big “cancer conspiracy” as something real.”
Agreed. The reason it seems that more people are getting cancer is that we live longer which gives cancer cells more time to start their mischief. The reason we don’t cure it is that it is an extremely complex set of diseases and none of us are God.
I cannot understand people who believe the “cancer conspiracy” propaganda. Do they really believe that people in the health industry are THAT evil? I could believe that about a government but I don’t believe it about healthcare and pharmaceutical companies.
Do they really believe that people in the health industry are THAT evil?
YES!
RE: drug companies aren’t interested in curing cancer any more than the cancer charities are.
First question that comes to mind when I read this -— aren’t he CEO’s and employees of drug companies people too? Don’t they have loved ones who have cancer?
If so, why should we think that they would value profit above the lives of their parents, wives or children?
The FDA controls the cancer industry. They control the testing and require Chemo (with destroys the immune system) before testing a patient with a new drug. I remember the FDA's 1970's war on Laetrile. I talked to a doctor from Mexico who saw cancer patients cured with it. And he had no financial incentive to tell me that.
They believe that many thousands of people go to work every day saying to themselves, "I know that my company is sitting on a cure for cancer, but I'm not going to mention it to anyone, just to protect my company's profit margins. To hell with my friends and relatives who are dying of cancer."
By the way, what ever happened to the 200 mpg carburetor? I guess the evil big oil companies must have succeeded in killing it.
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