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Weapons of mass destruction

MagazineMarch 2015 (Vol. 25 Issue 12)Weapons of mass destruction

The evidence is finally in that chemotherapy and radiotherapy both 'grow' cancer and cause it to spread, says Tony Edwards

The evidence is finally in that chemotherapy and radiotherapy both 'grow' cancer and cause it to spread, says Tony Edwards

When the history of conventional cancer treatment comes to be written, the year 2014 may mark the time when informed insiders finally realized the game was up-certainly for chemotherapy. That was when it finally became clear that the continuing failures of chemo weren't just due to the simple-minded barbarity of the treatment, but the fact that it is ultimately self-defeating.

On the face of it, that's odd. Almost every week, press stories quote medics, cancer charities, drug companies and the National Health Service confidently proclaiming that they're "winning the war on cancer" with new, advanced and increasingly costly chemotherapeutic agents. But how much of that is pure spin?

In late 2012, a group of "thought-leaders from across cancer research and treatment" assembled at a closed-door conference in Lugano, Switzerland, to try and answer that very question. The following year, those high-powered oncologists came clean about their deliberations and published a 5,000-word report in Europe's prestigious medical journal The Lancet.

It's worthwhile quoting their summary verdict in full. "The question was asked: are we winning the war on cancer?" they wrote. "The conclusion was, in general, no. Despite the introduction of hundreds of new anti-cancer drugs, including advanced therapies (so-called magic bullets) aimed at particular weapons in the enemy's armamentarium, the consensus was that, for most forms of cancer, enduring disease-free responses are rare, and cures even rarer. Notable exceptions include some forms of leukemia and certain types of breast cancer, testicular cancer, and particular tumours-e.g. colorectal-which are amenable in early stages to complete surgical removal." Straight from the horses' mouth, then: conventional cancer treatment has been a failure.

One obvious reason for this is that two of the weapons in medicine's armoury are not only toxic to cancers, but to healthy cells as well. Chemotherapy and radiation are given in the hope that they kill the cancer before they kill the patient. Another downside is that they damage the immune system, the very thing a healthy body relies on to keep cancer at bay.

The fact is, cancer cells are being created every minute of the day as part of normal living, and what stops them from taking hold are the natural killer and T cells generated by the immune system. So it seems somewhat perverse for medicine to have chosen modes of treatment that harm the body's own defences against the disease.

Such collateral damage inherent with the therapy undoubtedly contributes to cancer treatment's poor track record. Ten years ago, Australian cancer experts analyzed every clinical trial of some 22 different cancers treated by chemotherapy alone and estimated that chemo was responsible for the "5-year survival in adults [of] 2.3 per cent in Australia and 2.1 per cent in the USA".

And yet, as the five-year survival rate for cancer in Australia is "now over 60 per cent, it is clear that cytotoxic chemotherapy only makes a minor contribution to cancer survival", the authors wrote. "To justify the continued funding and availability of drugs used in cytotoxic chemotherapy, a rigorous evaluation of the cost-effectiveness and impact on quality of life is urgently required."

Another problem is that chemotherapy can actually cause cancer-at least in the long run, admits the American Cancer Society (ACS), the US's most conservative cancer organization (see box below and page 43). "Of all the possible late complications of cancer treatment, developing a second cancer is one of the most serious."

Over the past few years, teams of cancer researchers have been trying to discover why cancer drugs actually cause cancer. To their dismay, they've found that, just as a healthy body's immune system defends itself against bacteria and viruses, cancer itself has its own potent self-defence mechanisms-with predictable results.

Chemoresistance


When chemotherapy became the 'gold-standard' treatment of choice in the 1970s, it was thought that, as cancer cells grow more rapidly than healthy cells, poisoning the patient would likely mean the cancer cells would die first. And indeed they do-at least initially. And the cancer patient still has to survive the treatment.

Because chemotherapy infusions are so toxic, they can't be given in one hit without disastrous effects on the patient. That's why chemo is usually given in a series of six-week sessions, with a month's respite in between to allow the patient time to recover.

The trouble is, this treatment holiday turns out to be a godsend to cancer cells, which take advantage of the interlude to marshall their defences-and indeed, redouble them. Just as bacteria become resistant to antibiotics, cancer cells can become resistant to chemo.

"Resistance to therapy is not only common but expected," admit cancer experts. Although the mechanisms are different, with bacteria using the one simple survival-of-the-fittest technique, cancer cells have at least four ways to develop resistance.

The upshot is that chemotherapy regimes require the use of stronger and stronger toxins to combat the increasingly resistant cancer cells-to the increasing detriment of the patient's own healthy cells.

To make matters worse, it's recently been discovered that progressively toxic chemotherapy can create 'cancer stem cells'. Stem cells, currently touted as the miracle cells for regenerating everything from corneas to livers, are highly potent-and cancer stem cells are just as powerful. In fact, they're cancer's very foundation stones: cancer can't develop without stem cells. Worse still, cancer can't spread without stem cells-and it's the spread ('metastasis') that's the real killer of the disease.

"We have evidence that cancer stem cells are responsible for metastasis; they are the seeds that mediate cancer's spread," says Professor Max Wicha, director of the University of Michigan's Comprehensive Cancer Center. His team found that stem cells have a clever way of lying dormant, pretending to be other kinds of normal cells, then detaching themselves into the bloodstream to travel all over the body.

Having evaded chemotherapy by their effective mimicry, the stem cells settle in new areas, where they come back to life and rapidly divide to build new tumours.

Discoveries like these have set cancer researchers scrambling to work out why chemo seems to cause cancer and what to do about it. Doctors at the Memorial Sloan Kettering Cancer Center, New York's premier cancer research and treatment hospital, have uncovered one way in which chemotherapy can create cancer stem cells. "Although chemotherapeutic agents kill cancer cells," they say, "these treatments trigger a parallel . . . reaction leading to TNF- [tumour necrosis factor-alpha, a protein involved in cell-signalling] production, thus amplifying the 'paracrine loop' [cell-to-cell communication necessary for tumour cell migration] and causing chemoresistance; [this] provides a mechanism linking chemoresistance and metastasis."

Chemotherapy not only spreads cancer, but can also make the original tumour more invasive. It's been found that chemotherapy may inadvertently trigger a response called a 'DNA damage secretory programme' (DDSP). A detailed review describes DDSP as a "complex" and "robust" event in the body that promotes tumour progression "after treatment of cancer patients with DNA-damaging chemotherapy", causing changes in nearby surviving cells, "thereby stimulating malignant phenotypes of the tumour".
In plain English, chemotherapy makes healthy cells in the vicinity of a tumour turn cancerous.
But not all chemo damages DNA, so is there other, safer chemotherapy using simpler pharmaceutical toxins? Sadly no.

As another expert review informs us, "It is increasingly evident that in some tumours in which angiogenesis [new-vessel growth that feeds tumours] is thwarted pharmacologically, cancer cells adapt by migrating more aggressively into normal tissue", So, once again, chemotherapy makes healthy cells cancerous.

Cancer researchers have found a possible mechanism for this. Looking at tissues from patients given DNA-damaging chemotherapy, they discovered that healthy cells react with a 'damage response' that generates a cancer-stimulating protein called WNT16B.

"The increase in WNT16B was completely unexpected," Professor Peter Nelson of the Fred Hutchinson Cancer Research Center in Seattle told the press. "WNT16B, when secreted, would interact with nearby tumour cells and cause them to grow, invade and, importantly, resist subsequent therapy," he said. Such "enhanced tumour growth kinetics" would explain "the recovery and repopulation of tumour cells between treatment cycles [as] a major cause of treatment failure".

This offers solid evidence from the cutting edge of cancer research that the two main types of cancer-killing drugs can paradoxically cause cancer tumours to (1) grow and (2) spread throughout the body as metastases. The very same deadly paradox has now shown up in medicine's second anticancer weapon: radiotherapy.

Irradiating cancer


Trying to kill cancer cells by blasting them with ionizing radiation has been a mainstay of cancer treatment for decades. Like chemotherapy, the treatment kills both cancerous and healthy cells. But because radiotherapy can be targeted like a rifle on the tumour itself, it has generally been considered less harmful than the scattergun blunderbuss of chemotherapy.

Radiotherapy bombards cancer cells with gamma- or X-rays from a powerful radioactive source, causing total cell collapse by destroying cancer cell DNA. Side-effects in patients are thought to be minimal-mainly fatigue and localized skin burns. The long-term risk of secondary cancers is acknowledged, but considered rare and, on balance, worth it.

Yet, the latest evidence shows that the side-effects are much worse than once thought. In breast cancer treatment, for example, scientists at Leeds University found that radiation damage can cause endothelial cell damage, atherosclerosis, obstructed coronary arteries, thickened heart valves, fluid around the heart, inflammation of the pericardium (the sac surrounding the heart) and irregular heartbeat. "In some cases, [these] can occur up to 20 years post-treatment," they said.

And now radiotherapy has also been found to cause cancer-and not just over many decades, but relatively rapidly. A recent US survey found that 8 per cent of radiotherapy patients who managed to survive for at least a year developed "second solid cancers that could be related to radiotherapy"; of course, this figure doesn't include anyone who died within 12 months. In a related study of nearly half a million men, those who received radiation for prostate cancer had a 40 per cent additional risk of bladder cancer and an extra 70 per cent risk of rectal cancer.

And just like chemotherapy, radiotherapy can make those deadly cancer stem cells. The above-mentioned Seattle researchers found that radiotherapy can trigger the production of WNT16B, a protein that creates stem cells after chemotherapy, while a Harvard study found that low-dose gamma radiation was able to "induce stem cell-like properties in heterogeneous cancer cells".

So, radiotherapy can turn ordinary cancer cells into deadly stem cells that are not only "resistant to conventional chemo- and radio-therapies", but are also "ultimately responsible for tumour initiation, as well as cancer recurrence and metastasis". As they concluded, "In this study, we show that radiation can induce stem cell-like properties . . . with enhanced ability to self-renew, suggesting a novel mechanism for the radio-resistance commonly observed in human malignancies." Once again, cancer experts have openly admitted that radiotherapy often doesn't work and can actually cause cancer.

Combo drugs do no better


How has medicine responded to these bombshell findings? With radiotherapy, moves are already being made to reduce its use in breast cancer, which accounts for almost half of all radiation treatments. But because the prevailing cancer treatment model is so drug-centred, cancer experts find it difficult to think of any alternatives to chemotherapy. Their response to chemo's failures has been to experiment with the current drugs in various combinations in the hope of chancing upon a cocktail that might work better than the drugs on their own.

Sadly, this strategy is failing too, as a recent review admits. "Although many tumours present a satisfactory response when they are first exposed to chemotherapy, drug resistance occurs sooner or later in these tumours, and the majority of the patients develop progressive disease. Via a unique protection system, called multi-drug resistance, cancer cells can escape the toxic effect of most commonly used cancer drugs, in spite of their different chemical structures and different mechanisms of intracellular activity."

America's prestigious National Cancer Institute recently tested 5,000 random combinations of 100 chemotherapy drugs, hoping to find a winning formula for clinical use. Other researchers hope that drug companies will find more effective ways of killing cancer by attacking its stem cells, despite their particular resistance to current drug therapies.

As Dr Ian Mackenzie, professor of stem cell science at Barts Hospital in London, succinctly puts it: "The question is, how can you target cancer stem cells without damaging normal stem cells?"

The cure is worse than the disease


The 'attack the patient to kill the cancer' approach still seems to hold sway, even though half a century's experience shows that it's not only a dismal failure, but also a cause of the very disease it's meant to cure.

Although the focus of cancer innovators is on immunotherapy (see box, page 39), a few insiders are more radical. In a recent hard-hitting paper exposing the failure of conventional cancer treatment to achieve "high-level, consistent rates of disease-free survival for some of the most common cancers", Professor Sarah Crawford of the Cancer Biology Research Laboratory in Connecticut pleaded for "a new paradigm" of treatment incorporating both "anti-inflammatory and antioxidant therapeutics".

Such an approach is what holistic medicine has always advocated: to prevent cancer, follow a healthy way of life supported by good nutrition, but if you're unlucky enough to get cancer, choose treatments that bolster the body's own natural anticancer defenses. After all, it's only logical, isn't it?

Growing cancer stem cells


How do these wily, highly dangerous, cancer stem cells arise? The recent bombshell discovery is that stem cells can be created by chemotherapy itself. Professor Wicha's Michigan group gave the chemotherapy drug Avastin to mice and found that, although the drug initially shrank their breast cancer tumours, the effect was short-lived: the cancers returned with a vengeance and spread because the mice treated with chemotherapy had developed cancer stem cells.

"This study provides an explanation for the clinical trial results demonstrating that, in women with breast cancer, agents such as Avastin delay the time to tumour recurrence but do not affect patient survival," says Wicha.

Last December, scientists at Johns Hopkins University reported much the same thing with another breast-cancer drug. "Our study showed that the chemotherapy drug paclitaxel . . . enhances the survival of breast cancer stem cells, which are the cancer cells which must be killed to prevent relapse and metastasis," said team leader Dr Gregg Semenza.

Live to have another cancer


Doctors are reluctantly admitting that chemotherapy can cause cancer. Here are a few of the cancers linked to chemo and other anticancer drug treatment.

o Acute myelogenous leukaemia (AML), chronic myelogenous leukaemia (CML) and acute lymphoblastic leukemia (ALL), says the ACS, are all linked to "past radiation exposure" which, when added to chemo, raises cancer risk even further.

o Breast cancer can be made worse
by tamoxifen, a man-made oestrogen-blocking drug commonly given to treat breast cancer, as tumours have been found to shrink when the drug is stopped.

o Endometrial cancer risk can also increase with tamoxifen to about one in every 500 breast cancer patients using the drug.

o Secondary tumours may be caused by some chemo drugs. Harvard Medical School researchers showed that imatinib and sunitinib, for example, after initially shrinking primary cancer tumours, caused a threefold increase in secondary tumours. As Professor Raghu Kalluri, the study's chief author, told the press: "If you just looked at tumour growth, the results were good. But when you looked at the whole picture, inhibiting tumour vessels was not controlling cancer progression. The cancer was, in fact, spreading."

Boost the body to kill the cancer


Recognizing that cancer is kept at bay by the immune system, some cancer researchers believe it makes sense to find treatments that boost immunity rather than the opposite-such as what chemotherapy does in the body.

One new cancer immunotherapy involves the patients growing more T cells, boosting them with a specific anticancer antigen and injecting them back into the body. One team at the Children's Hospital of Philadelphia used the technique on children with severe leukaemia-with considerable success. "The children's cancers were so aggressive they had no treatment options left," said team leader Stephan Grupp. "The durable responses we have observed with the therapy are unprecedented."

In fact, the case for immunotherapy appears to be gaining ground within the cancer establishment. Researchers at Johns Hopkins University School of Medicine point out that, compared with the damage caused by conventional chemotherapy, "immunotherapies are active and dynamic, and capable of inducing immune memory to propagate a successful rebalancing of the equilibrium between tumour
and host". In other words,immunotherapy works to support Nature's balancing act of inadvertently producing cancer cells, but then immediately destroying them.

Cancer diagnostics that cause cancer


Mammograms
Cancer's most common diagnostic screening procedure involves squeezing the breast between two X-ray plates, a technique that hasn't changed much in half a century-except to reduce the X-ray dose that itself causes cancer. Even so, for every 10,000 women who have three-yearly mammograms, an estimated three to six women will get breast cancer as a direct result of the radiation. These figures come from the very 'establishment' Cancer Research UK, so it's almost certainly an underestimate.

Although once claimed to be a vital part of cancer medicine, mammography is now under increasing critical scrutiny. Many studies, like the recent 25-year survey in Canada, have found that breast cancer screening doesn't reduce death rates. Worse, mammography may even increase deaths, according to a Danish study of nearly 60,000 women who had undergone mammography. Those wrongly identified as having breast cancer (so-called 'false positives') were at significantly greater risk of developing breast cancer later on than women originally given the all-clear.

One reason for this may be that a positive mammogram often leads to a cascade of further tests, procedures and treatments, all of which have health risks. Add to that the emotional trauma of a cancer diagnosis, which increases stress (cortisol) levels, and you have an immune system with a reduced capacity to fight cancer.

Biopsy
This investigation, which involves puncturing the suspected tumour to obtain a tissue sample, has long been suspected of causing cancer to spread by 'seeding'. One investigation into a California hospital's medical records showed that needle biopsies to test for breast cancer were linked to subsequent metastases.

A more recent review of 25 years of research concluded that, although tumour seeding does happen, it's at "a microscopic level, the clinical effect appears negligible, and biopsy as a cause of disease recurrence appears very rare". Nevertheless, the authors recommend ditching needle biopsy for vacuum-assisted devices, considered 'safer', so draw your own conclusions.

Biopsies performed elsewhere in the body are even more of a problem. One major US military hospital reported that as many as 1 per cent of their prostate patients died as a result of biopsy-seeded prostate cancer. Last year, a review of 25 years of clinical experience reported cases of cancer spreading after biopsy of the liver, abdomen and mouth.

Safer alternatives
For suspected breast cancer, choose thermography (see www.iact-org.org) and ultrasonography. Up-and-coming technologies like microwave tomography and ImagioTM (a hybrid ultrasound/sound-and-light, or 'opto-acoustic', device) aim to replace biopsy.

Promising alternatives


Homeopathy
Considerable success is claimed for the Banerji method, which uses combinations of homeopathic remedies. A recent audit found that "complete regressions ranged from 22 per cent to 32 per cent . . . for lung, brain, and oesophageal cancer" in homeopathic hospitals in India.

Vitamin C
Championed by Nobel Laureate Linus Pauling, apart from its nutritional value, vitamin C turns into hydrogen peroxide, which "can be detrimental to certain tumour cells". However, clinical trials of intravenous infusions are few and have had mixed outcomes.

Ozone therapy
This is largely inspired by Nobel Prize-winner Dr Otto Warburg's theory that, as cancer is caused by a lack of oxygen, it will regress in the presence of oxygen. Ozone (oxygen plus an extra oxygen atom) destroys cancer cells, but not healthy ones. An audit of the Hufeland Clinic in Germany, where ozone is used along with other complementary therapies, showed remarkable benefits. The therapy lacks formal clinical trials, though.

Citrus

"Citrus limonoids are . . . potent inhibitors of . . . human breast cancer cells in culture", Canadian researchers reported a few years ago in just one of many experimental studies showing "growing evidence supporting the beneficial action of citrus flavonoids on multiple cancer-related biological pathways", while being harmless to healthy cells. Human clinical trials are still some way off, although one Japanese company makes a citrus-peel extract called Gold Lotion, which showed potent anticancer actions in animal studies.

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