Another Fine Mess


Did you guess from the title that this short piece is about the seeming inability of the British Government to run well, most things but especially IT programmes? Of course you did! Provoked by the latest National Health Service furore. In case you’ve been away with the fairies for a bit, a major cock-up in its computer system has just come to light whereby, between 2009 and 2018, it failed to invite 450,000 women between the ages of 68 and 71 for breast screening. Secretary of State for Health, Jeremy Hunt (our man usually on hand with a can of gasoline when there’s a fire), told Parliament that “there may be between 135 and 270 women who had their lives shortened”. Cue: uproar, headlines: HUNDREDS of British women have died of breast cancer (Daily Express), etc.

Logo credit: Breast Cancer Action

I’ve been reluctant to join in because I’ve said all I think is worth saying about breast cancer screening in two earlier pieces (Risk Assessment and Behind the Screen). Reading them again I thought they were a reasonable summary and I don’t think there’s anything new to add. However, this is  a cancer blog and it’s a story that’s made big headlines so I feel honour-bound to offer a brief comment — in addition to sympathizing with the women and families who have been caused much distress.

My reaction was that Hunt was misguided in mentioning specific numbers — not only because he was asking for trouble from the press but mainly because the evidence that screening itself saves lives is highly questionable. For an expert view on this my Cambridge colleague David Spiegelhalter, who is Professor for the Public Understanding of Risk, has analysed the facts behind breast screening with characteristic clarity in the New Scientist.

Anything to add?

I was relieved on re-reading Risk Assessment to see that I’d given considerable coverage to the report that had just come out (2014) from The Swiss Medical Board.  They’d reviewed the history of mammography screening, concluded that systematic screening might prevent about one breast cancer death for every 1000 women screened, noted that there was no evidence that overall mortality was affected and pointed out that false positive test results presented the risk of overdiagnosis.

In the USA, for example, over a 10-year course of annual screening beginning at 50 years of age, one breast-cancer death would have been prevented whilst between 490 and 670 women would have had a false positive mammogram calling for a repeat examination, 70 to 100 an unnecessary biopsy and between 3 and 14 would have been diagnosed with a cancer that would never have become a problem.

Needless to say, this landed the Swiss Big Cheeses in very hot water because there’s an awful lot of vested interests in screening and it’s sort of instinctive that it must be a good thing. But what’s great about science is that you can do experiments — here actually analysing the results of screening programmes — and quite often the results turn to be completely unexpected, as it did in this case where the bottom line was that mammography does more harm than good.

This has led to the recommendation that the current programmes in Switzerland should be phased out and not replaced.

So we’re all agreed then?

Of course not. In England the NHS recommendation remains that women aged 50 to 70 are offered mammography every three years — which is just as well or we’d have Hunt explaining the recent debacle as new initiative. The American Cancer Society “strongly” recommends regular screening mammography starting at age 45 and the National Cancer Institute refers to “experts” that recommend mammography every year starting at age 25 for women with mutations in their BRCA1 or BRCA2 genes.

The latter is really incredible because a study published in the British Medical Journal in 2012 found that these mutations made the carriers much more vulnerable to radiation-induced cancer. Specifically, women with BRCA 1/2 mutations who were exposed to diagnostic radiation (i.e. mammography) before the age of 30 were twice as likely to develop breast cancer, compared to those with normal BRCA genes.

They are susceptible to radiation that would not normally be considered dangerous because the two BRCA genes encode proteins involved in the repair of damaged DNA — and if that is defective you have a recipe for cancer.


So it’s probably true that the only undisputed fact is that we need much better ways for detecting cancers at an early stage of development. The best hope at the moment seems to be the liquid biopsy approach we described in Seeing the Invisible: A Cancer Early Warning System? but that’s still a long way from solving a general cancer problem, well illustrated by breast mammography.


In the beginning … 

You may have noticed that the American actress Angelina Jolie, who is now employed as a  Special Envoy  for the  United Nations High Commissioner for Refugees, has re-surfaced in the pages of the science media. She first hit the nerdy headlines by announcing in The New York Times that she had had a preventive double mastectomy (in 2013) and a preventive oophorectomy (in 2015).

We described the molecular biology that prompted her actions in A Taxing Inheritance. The essential facts were that she had a family history of breast and ovarian cancer: genetic testing revealed that she carried a mutation in the BRCA1 gene giving her a 87% risk of breast cancer and a 50% chance of getting ovarian cancer.

A star returns

BRCA1 and breast cancer are back in the news as a result of a paper by Jane Visvader, Geoffrey Lindeman and colleagues in Melbourne that asked a very simple question: which type of cell is driven to proliferate abnormally and give rise to a tumour by mutant BRCA1 protein? That is, pre-cancerous breast tissue contains a mixture of cell types: does cancer develop from one in particular –  and, if you blocked proliferation of that type of cell, could you prevent tumours forming?

Simple question but their paper summarises about 10 years of work to come up with a clear answer.

And the villain is …

The mature mammary gland is made up of lots of small sacs (alveoli) lined with cells that produce milk – called luminal cells. Groups of alveoli are known as lobules, linked by ducts that carry milk to the nipple. Most breast cancers start in the lobular or duct cells.

Breast fig copy

Left: Normal breast lobule showing alveoli lined with milk-producing luminal cells connected to duct leading to the nipple. Right: Normal milk sac, non-invasive cancer, invasive cancer.

Things are complicated by there being more than one type of progenitor cell but the Melbourne group were able to show that, in mice carrying mutated BRCA1, one subtype stood out in terms of its cancerous potential. These cells carried a protein on their surface called RANK (which is member of the tumour necrosis factor family). They had gross defects in their DNA repair systems (so they can’t fix genetic damage) and they’re highly proliferative. Luminal progenitors that don’t express RANK behave normally.

Slide1 copy

Scheme representing normal and abnormal cell development. The basic idea is that different types of cells evolve from a common ancestor. The Australian work identified one type of luminal progenitor cell that carries a protein called RANK on its surface (pink cell) as being a prime source of tumours. RANK+ cells have defective DNA repair systems so they accumulate mutations (red cells) more rapidly than normal cells, a feature of tumour cells.

In mice with mutant BRCA1 a monoclonal antibody (denosumab) that blocks RANK signalling markedly slowed tumour development. In a small pilot study blockade of RANK inhibited cell proliferation in breast tissue from human BRCA1-mutation carriers.


How effective blocking the activation of RANK signalling will be in preventing breast cancer is anyone’s guess but the idea behind the work of the Australian group cannot be faulted. Being able to prevent the ‘starter’ cells from launching themselves on the pathway to cancer driven by mutation in BRCA1 would mean that women in Angelina Jolie’s position would not have to contemplate the drastic course of surgery. The question is: will the preliminary mouse results lead to something that works in humans and, moreover, does so with high efficiency. As ever in cancer, watch this space – but don’t hold your breath!


Nolan, E. et al. (2016). RANK ligand as a potential target for breast cancer prevention in BRCA1-mutation carriers.


Cancer Genetics: Never Black or White

The National Heath Service occupies a uniquely revered place in the psyche of the British people – as indeed it should, the concept of free, first rate health care available when required being one of the hallmarks of civilization. Founded in 1948, the NHS has continued to this day to fulfill its remit with astonishing efficiency in the face of demands beyond comprehension sixty years ago, as both the size of the population and life expectancy have increased and medical practice has been transformed by technical advances. Even so, there is one area in which there is a surprising shortfall in the performance of the NHS when compared with most other European countries or with the USA – cancer survival rates.

We’re behind you!!

Broadly speaking, the latest findings of a massive study (called CONCORD-2, a long-term global comparison of cancer survival) show 5-year cancer survival rates in the UK for 2005 to 2009 to have been worse than they were in many European countries at least a decade earlier. “Shameful” cried Macmillan Cancer Support – rarely a helpful response but you have to concede it’s scarcely grounds for an outbreak of British smugness. More to the point, Cancer Research UK insisted the gulf was often linked to deprivation, i.e. patients in poorer areas tend to live unhealthy lifestyles so they are more susceptible and likely to be diagnosed later. This refers to what has become known as the postcode (zipcode) lottery whereby the chances of being diagnosed early and surviving various forms of cancer differ significantly (meaning as much as two-fold!) across the UK. Further contributions come from general practitioners missing the early signs of cancer, adding to the delay in referral, together with variable standards of treatment.

And the answer is?

But hang on! None of this actually explains why these problems should be more acute in the UK than in, say, France or Finland who presumably have their share of the poor and incompetent. So what might be different in the UK? Here’s my theory. Maybe it’s just us, the Jane & John Does lining up to become cancer patients. Dentists reckon they can pick Brits from Yanks just by peering into their oral cavities (Brits have cavities {ho ho} whereas Americans are perfect – tooth-wise that is). Why? Because we don’t care: we figure our bodies are non-maintenance machines – so we never dream of getting them serviced, that is, having regular check-ups – and when they do conk out we expect the wondrous NHS to fix it. To see if there’s any truth in this theory I conducted a meaningless, random poll in my department (featuring two Americans, one Finn, a Dutchman, two German ladies and a French girl – all from nations that do better than the UK) asking ‘how health aware are your countrymen compared with the British?’ Result? They’re all hypochondriacs compared to Brits whose default method is to avoid doctors until they’re at death’s door. So there we have it: it’s our fault and if we just looked after ourselves a bit better the UK would scrabble its way up the cancer survival league.

Sounds familiar?

Take the specific example of breast cancer. 81% of UK women diagnosed between 2005 and 2009 were alive five years later but in Sweden, France and Italy the rates range from 86 to 87%. This kind of gap is reminiscent of that in the USA between African American women and those of European descent – presently 79% versus 92 % – a disparity that has remained pretty constant over the last 40 years even though the survival rates of both groups have steadily risen (the overall USA survival rate for breast cancer is now 89%). Again the divide has been attributed to poverty and education level, together with lack of health insurance, so that detection is delayed and survival times shortened.

So it’s clear that multiple factors contribute to the variable treatment success rates but so far there’s no evidence that genetic differences play a part, for example, by giving rise to more aggressive forms of cancer.

A little more light in one corner

Breast cancers are an enormously varied set of diseases and as such they’re a challenge even to classify yet alone to treat. The recent rapid progress in DNA sequencing has led to a new genome-based classification system but there is still strong reliance on the traditional prognostic and predictive factors, notably what’s called hormonal status – meaning presence on the surface of the tumour cells of the protein receptors to which the hormones oestrogen and progesterone attach, together with the presence or otherwise of the human epidermal growth factor receptor 2 (HER2). One significant sub-group has no detectable levels of these proteins – they’re ‘triple negative’ – and they make up 10-15% of breast cancers (TNBCs). TNBCs are very aggressive cancers (poor prognosis), known for some years to disproportionally affect young women of African origin – it’s about twice as common in African Americans as in European Americans.


The triple negative breast cancer survival rate dependence on race.

African-American women with TNBC have poorer survival rates than women of European descent (Dietze et al., 2015).

Step forward DNA sequencing – again!

What wasn’t known was anything by way of explanation of these epidemiological findings but from sequencing tumour DNA it has emerged that mutations in BRCA1 are present in most (69%) of TNBCs in women of European origin. Inherited mutations in BRCA1 are particularly associated with breast and ovarian cancers, as we explained in a recent item on Angelina Jolie (A Taxing Inheritance). But here’s a very odd thing: African-American women have a low incidence of BRCA1 mutations (less than 20%), despite the fact that they are relatively prone to TNBC.

What’s new?

Well, if BRCA1 isn’t doing the driving there must be other potent drivers for TNBC and the new genetic studies have given us one more piece in the molecular jigsaw of cancer. However, to take up Frances M. Visco’s point in a recent letter to The New York Times and one that I have made forcefully elsewhere (in Not another ‘Great Cancer Breakthrough’!!! and Gentlemen! For goodness’ sake …), this is not another ‘breakthrough’ yet alone a ‘great one.’ It won’t save lives until we identify what the other drivers are and come up with a therapeutic ploy to exploit our knowledge.

Right on cue, step forward Alex Swarbrick, Simon Junankar and colleagues from Sydney’s Garvan Institute of Medical Research who have just found that a protein called ID4 appears to control some TNBCs: it’s present at high levels in about half of all TNBCs. ID4 stands for ‘inhibitor of differentiation 4′ which means that it keeps cells in a state where they can continue to divide – a hallmark of cancer.

So now it’s over to the lads from down under to do the difficult bit and come up with an inhibitor of ID4 – and to show that it works to stop TNBCs in their tracks.


Allemani, C. et al., (2015). Global surveillance of cancer survival 1995-2009: analysis of individual data for 25 676 887 patients from 279 population-based registries in 67 countries (CONCORD-2). Lancet 385, 977-1010.

Dietze, E. et al., (2015). Triple-negative breast cancer in African-American women: disparities versus biology. Nature Reviews Cancer 15, 248–254.

Junankar, S. et al., (2015). ID4 controls mammary stem cells and marks breast cancers with a stem cell-like phenotype. Nature Communications 6, Article number: 6548 doi:10.1038/ncomms7548.


Lethal Lifesaver

Almost exactly three years ago (goodness me, it seems like a couple of months!) I wrote a piece about one of the novel approaches to cancer therapy being tried around the world. This exploits an effect called synthetic lethality that refers to the death of a cell as a result of a combination of mutations in two or more genes whilst mutation in either of these genes alone leaves the cell perfectly functional. The example involved two distinct pathways that repair damaged DNA – recall that our genetic material is being continuously assaulted in a variety of ways and that we’ve evolved very effective repair strategies. One of these involves a pair of familiar ‘cancer genes’, BRCA1 and BRCA2, mutated forms of which can be inherited to give rise to several types of cancer. The other requires an enzyme called PARP (for poly (ADP-ribose) polymerase). So the idea is that if BRCA mutations block that route the cell becomes dependent on PARP. Stop PARP functioning and the cell accumulates genetic damage that it is eventually unable to live with. Result: death of a cancer cell.

Blog fig

Synthetic lethality. If there are two distinct signaling pathways in a cell, each of which can be blocked without harming the cell but when both are inhibited simultaneously the cell dies, the effect is called synthetic lethality. The enzyme PARP (poly (ADP-ribose) polymerase 1) normally repairs single-strand DNA breaks. When this pathway is blocked by PARP inhibitors single-strand DNA breaks accumulate together with double-strand DNA breaks. If cells have normal BRCA, the double-strand breaks are repaired by a second pathway involving BRCA and the cell survives. However, in cancer cells with mutant BRCA this pathway is impaired. The use of PARP inhibitors means that neither pathway can work and the inhibitors, in effect, selectively target and kill cancer cells with BRCA mutations.

‘Three cancers for the price of one’ summarized small-scale clinical trials of several related PARP inhibitors, including one called olaparib, treating breast, ovarian and prostate cancers (BRCA mutations cause about 5% of breast cancers and 10% of ovarian cancers and they can also give rise to prostate cancer). The drugs showed effects on all three tumour types but in a subsequent trial there was no significant survival benefit for breast cancer patients.

Whilst that was a set-back I was sufficiently prescient to comment that ‘the PARP story is far from over’ and indeed further trials have shown significant effects on ovarian cancer, olaparib prolonging progression free survival from 4.3 months to 11.2 months. On this basis  Lynparza (aka Olaparib) was approved in December 2014 in both Europe and the USA for the treatment of advanced ovarian cancer with mutated BRCA.

This is only one more small step along the road to equipping us with a comprehensive anti-cancer drug cabinet but it is, of course, good news for the patient group who should benefit. For my colleague Steve Jackson and his team who developed this approach it must be a wonderful moment and they can look forward to following the success of the drug, now being marketed by Astra-Zeneca.

A Taxing Inheritance

The centenary of the beginning of the First World War prompted me, as perhaps many others, to reflect on how successive generations have done since then in terms of what they’ve bequeathed to their offspring. I didn’t need to think for too long though, to find myself muttering ‘Thank heavens for science’—because most of the rest is a pretty dismal chronicle. I know, not all technological advances in the past one hundred years have been a cause of unrestrained joy but many of them transformed life in the most wonderful ways. Would that we could point to such success in other fields.

Our best defence may be to aver: “Man cannot control the current of events. He can only float with them and steer”, a saying attributed to Otto von Bismarck. If the ‘Iron Chancellor’ actually did utter those words it seems to me he was being coy beyond belief. He is, after all, generally credited with unifying Germany, seeing off the last French monarch (Napoleon III) and establishing the peaceful domination of Europe by the German Empire that lasted until long after his death—and setting up the first welfare state along the way. “The main thing is to make history, not to write it” sounds much more like Bismarck in full and frank mode.

Nature and Nurture

One form of history that we do write but indeed we cannot control comes in the form of the genetic material that we pass to the next generation. We’re all familiar with some of this legacy because we literally see it in physical resemblances and other attributes between parents and children (“He’s got his Mum’s eyes”) or shared by siblings (“Jack and Jill are wonderful musicians”). They’re shared because large chunks of the genetic code (i.e. DNA) are identical between the individuals concerned. But if conserved DNA makes for similarities, what of the differences—the fact that our parents and brothers look different to all the seven thousand million other people on the planet? Our unique features come from variations in the genetic code—odd changes in the units (bases) of DNA scattered through our genome. Called SNPs (pronounced ‘snips’ for single nucleotide polymorphisms), they’re what make the differences between us. In other words, a SNP is a difference in a single nucleotide—A, T, C or G—within a stretch of DNA sequence that is otherwise identical between two individuals. For example, you have AAGCCTA whereas I have AAGCTTA. These genetic variations that make individuals different are the basis of DNA fingerprinting.

There’s about three million SNPs scattered throughout the human genome (so, on average, you’d come across one in every 1,000 bases if you scanned your DNA from beginning to end) and they’re what makes each of us unique. Within ethnic groups common patterns of such variants confer characteristics (dark skin/light skin, tall/short, etc) and, with that in mind, you might guess that there will also be variants that make such groups more (or less) susceptible to diseases.

Of course, there’s an endless debate about the border between our genetic inheritance and how the world we experience makes us what we are—how much of Jack and Jill’s precocious talent is because Mum and Dad made them practice twelve hours a day from age five? Fortunately we can ignore nurture here and stick to genes because we’re trying to pin down the good and the bad of our genetic legacy.

What’s all this got to do with cancer?

A good bit is that we’re distinct from everyone else but still share family features. However, our genetic baggage may also contain some unwanted freebies—the most potent of which can give a helping hand to a variety of diseases, including cancers. Cancers are caused by damage to DNA—a build-up of changes, i.e. mutations, that affect the activity of proteins critically involved in controlling cell growth. For most cancers (90%) these mutations accumulate over the lifetime of the individual—they’re called “somatic mutations”—so you can’t blame anyone but yourself and Lady Luck. But about 10% get a kind of head start when someone is born with a key mutation. That is, the mutated gene came from either egg or sperm (so it’s a germline mutation). This effect gives rise to cancers that “run in families”: a critical mutation is passed from generation to generation so that children who inherit it have a greatly increased risk of developing cancer. Two of the most common cancers that can come in hereditary form are those of the breast and bowel.


A mutational steeplechase leads to cancer. Of the tens of thousands of mutations that accumulate over time in a cancer cell, a small number of distinct “drivers” make the cancer develop (four are shown as Xs). Almost all mutations arise after birth, but about one in every ten cancers start because a person is unfortunate enough to be born with a mutation: they are already one jump ahead and are much more likely to get cancer than those born with a normal set of genes. The rate at which mutations arise is increased by exposure to carcinogens, e.g., in tobacco smoke.

Breast cancer is about twice as common in first-degree relatives of women with the disease as it is in the general population (you’re a first degree relative if you’re someone’s parent, offspring, or sibling). About 5% of all female breast cancers (men get the disease too but very rarely—about 1% of all breast cancers) arise from inherited mutations. In the 1990s two genes were identified that can carry such mutations. These are BRCA1 and BRCA2 and their abnormal versions can increase the lifetime risk of the disease to over 50%, compared with an average of about 10%. Since then heritable mutations in some other genes have also been shown to increase the risk.

Angelina Jolie

Angelina Jolie

A star turn

Breast cancer genetics came under the spotlight with the much-publicised saga of Angelina Jolie, the American film actress. Jolie’s mother and maternal grandmother had died of ovarian cancer and her maternal aunt from breast cancer—a family history that persuaded Jolie to opt for genetic testing that indeed revealed she was carrying a mutation in BRCA1 (BRCA1 and BRCA2 mutations account for about 10% of breast cancers and 15% of ovarian cancers). For Jolie the associated lifetime risk of breast cancer was estimated as 87%, prompting her to have a preventative double mastectomy, thereby reducing her risk to less than 5%. The months after she revealed her story saw the “Angelina effect”, a doubling in the number of women being referred for genetic testing for breast cancer mutations.

What’s all this got to do with SNPs?

The story so far is of the one in ten cancers that get kicked off by a powerful, inherited mutation that changes the action of the affected protein—the BRCAs being the best-known examples. However, the BRCAs and other known mutated genes account for only about 25% of familial breast cancers, meaning that for three quarters of cases the genetic cause remains unknown. And yet we know there is an inherited (genetic) cause simply because of the generational thread. Which brings us back to those other, more subtle tweaks to DNA that we mentioned—SNPs—alterations that don’t directly affect proteins, so they’re often called variants to distinguish them from mutations.

It seems very likely that the missing culprits are indeed SNPs—lots of them. These DNA variants each make a contribution so small that on its own would have no detectable effect on the chances that the carrier will get cancer. Their impact comes from a cumulative effect. They’re like pieces of straw, individually easily bent or broken but put a dozen of them together and you have a rope. Thus combinations of individually insignificant SNPs can raise the risk of cancer by, say, 10%—not a massive increase but not negligible either. Twins who are genetically identical have similar risks of developing breast cancer, consistent with the idea that many variants, each having a very small effect, can combine to give a substantial increase in risk. Very slowly, by sequencing lots of genomes, these rare variants are being identified. Given that clusters of appropriate variants confer risk, people with the “other” variant have, in effect, a degree of protection against cancer.

And in our more distant relatives?

All this comes from the huge effort that has gone into finding genetic variants linked to one of the most common cancers but, unsurprisingly, almost all the attention has focused on European women. Not before time, someone has got round to looking for breast cancer variants in East Asians who, after all, make up over one fifth of all the people in the world. Cai Qiuyin and his colleagues at the Vanderbilt University School of Medicine compared the genomes of over 20,000 cancer cases from China, Japan and South Korea with a similar number of disease-free controls. After much selecting and comparing of sequences, three particular DNA variants consistently associated with significant cancer risk. The variants were much less common in European women, suggesting that as the DNA keyboard has been strummed by evolution, distinct patterns associated with breast cancer have emerged in diverse populations.

Just two problems then. First it’s a huge task to assemble the lists of runners (and as the Asian results show, they will differ between ethnic groups). But the real challenge is yet to come. Almost all of these variants (99.9%) don’t change the sequence of proteins (i.e. how the proteins work). What they do is exert subtle effects on, for example, how much RNA or protein is made from a DNA gene at any time. At the moment we have little understanding of how this works, yet alone ideas on how to intervene to change the outcome.

Although identifying the BRCA genes that help to drive breast and ovarian cancers was a giant breakthrough, we still have no effective therapy for countering their malign influences. The intervening twenty-five years of effort have brought us to a new era of revealing the more subtle effects of variants. But the price we pay for unveiling the complete picture is perceiving just how tough is the therapeutic challenge.


Qiuyin Cai, et al. (2014). Genome-wide association analysis in East Asians identifies breast cancer susceptibility loci at 1q32.1, 5q14.3 and 15q26.1. Nature Genetics 46, 886–890. doi:10.1038/ng.3041.

Three cancers for the price of one?

Damaging the DNA Double-helix

A colleague of mine works on double-stranded DNA repair, as it’s called in the trade. This is something that goes on in all of us as our cells patch up DNA that’s being continuously assaulted by things that cause mutations. One source of damage is radiation that can snip the double helix, leaving separate bits of chromosomes floating around in the nucleus. Anything involving ‘snipping’ suggests a pretty potent type of mutation and it does indeed present a real problem because the cell has to find ways of tagging the floating ends, bringing them together and stitching them up. Amazingly, Nature has come up with not one but several ways of doing this and, by and large, they work pretty well. In ferreting around to define the proteins involved, my friend and his team also tried out drugs that might block repair. Having found a very effective one they set up a company to develop it – duly taken over by AstraZeneca, with the result that I now know one person in science who is very rich. The hope is that the drug might work against ovarian, prostate and breast cancers – which would be very good news for AstraZeneca!

But, you may already be asking, what’s the use of a repair blocker? Surely that’s the last thing you want in staving off cancer? Well, yes – and no. All things being equal, you do want to keep repair systems working but, if one of them becomes defective as part of cancer development, knocking out another may push the cell over the brink so that it can’t deal with the DNA chaos and commits suicide.

Bear in mind that our picture of cancer is one of widespread damage to DNA. But the genetic anarchy of cancer has parallels with the political variety in that both have limits. If the Molotov cocktail fraternity so disrupt society that the binmen stop collecting rubbish, everyone dies of cholera – not exactly a great social reform. Cancer too walks a tightrope between the disruption needed to overcome normal cell control and an extreme level of chaos that would simply kill the cell.

Two of the most familiar ‘cancer genes’ are BRCA1 and BRCA2, mutated forms of which can be inherited to give rise to several types of cancer. It turns out that both BRCAs play roles in DNA repair. The drug that has improved my friend’s bank balance is olaparib and it targets another DNA repair pathway – involving an enzyme called PARP (for poly (ADP-ribose) polymerase). So that’s why it’s useful: if the BRCA route is already blocked by mutation, inhibiting a second repair pathway (PARP) may scupper the cancer cell.

BRCA mutations cause about 5% of breast cancers and 10% of ovarian cancers and they can also give rise to prostate cancer. Small-scale clinical trials of olaparib and several related PARP inhibitors have shown anti-tumour effects against all three of these cancers. However, the most recent trial showed no significant effect on survival of breast cancer patients. Whilst this is a set-back for the PARP inhibitor field, another trial has shown significant effects on ovarian cancer.

As so often in the history of cancer treatment, great expectations have taken a bit of a knock but the PARP story is far from over and it still holds the promise than one class of drugs may be effective against several different types of cancer. If it were to turn out that way it would be great news for some cancer patients – and not bad for one or two bank balances.