Thursday, 24 September 2015

Effective killers: liver cancer

The liver is an extraordinary organ.  It weighs about the same as your brain but is far more alive.  From the time you're old enough to vote, your brain is getting smaller all the time as neurons die off at the rate of 10,000 per day. After the age of, say, 80 so little remains that it rattles about in your head like a pea in a drum.  If you have a fall now what's left is likely to accelerate hard against the inside edge of your skull and kill you quicker than contact sport encephalopathy.

The liver OTOH has remarkable capacity for regeneration and seems to turn over its cells even as it maintains the same overall shape. If you require a liver transplant you're likely to get a stump of donor liver rather than the whole thing because it's easier to insert. From as little as 25% of the mass, a complete liver can be regenerated in a short time. It's the nearest thing we have to a salamander's tail. Being this much programmed to grow is something of a double-edged sword because the liver is also very prone to cancer and, unless your oncologist gets in there very early with the knife and aggressive chemo- and radiation-therapy, your prognosis is not good. The US five-year survival rate after a liver cancer diagnosis is as low as 16.6% while in the UK 80% are dead within a single year.  I'm getting all this from a really readable 16 page supplement in Nature from 4th December 2014. [Sorry, it's pay-walled, ordinary people]

Liver cancer doesn't always follow from other liver disease but it never seems to happen unless there is a pre-existing condition: viral infection by HCV or HBV, alcohol-induced cirrhosis, fatty-liver disease or fungal toxins, like aflatoxin, from the diet. Where you live determines which of these triggers is prevalent. Hepatitis C Virus HCV infects 180 million people across the world but the rate is far higher in Egypt than anywhere else. 350 million have HBV in their livers but it is much more common in East Asia [10%; 120 million Chinese] than The West [0.5%].  Indeed, the UK government has decided it is not cost effective to institute wide-spread vaccination of the citizenry, although an effective vaccine exists and is making a huge dent in the spread of the disease in the third world.

With 800,000 new cases of liver-cancer being diagnosed each year and no sign that the number is diminishing, there is a huge pot of money for BigPharma to play for.  There is only one effective therapy against hepatocellular carcinoma HCC which is approved by the FDA: Sorafenib [Bayer/Onyx] which acts by inhibiting key enzymes called tyrosine kinases. TKs are signalling molecules and there are lots of them which talk to each other to make biochemical things happen.  The two main processes needed by growing tissue, like a carcinoma, are cell division and better blood-supply to deliver fuel to the dividingcoal-face.  Both of these depend on a cascade of TKs which are seemingly inhibited by Sorafenib.  The problem is that we only have 23,000 protein coding genes to play with, so all these signalling molecules have to double-up and triple-up their roles. If inhibiting cell division in the liver is desired, you want to make damned sure you're not inhibiting cell-division in the bone-marrow or you'll have no white-blood-cells to fight the cancer.  That's the sort of thing that gets labelled 'side-effects'.

"effective" should be taken 3 times daily with a pinch of salt because Sorafenib costs $5400/month and will likely win you only 3 months of extra time to put your affairs in order. Remind me not to bother: $5400x3 = $16,000 is tuition, room and board and extra tango lessons for the grand-child's first year in college [in Ireland, I'm not imagining Harvard here]. The Pharmaceutical herd is not far behind Bayer with their me-too drugs Linifanib [AbbVie]; Brivanib [BristolMyers]; Sunitinib [Pfizer] which act in essentially the same way and are unlikely to be any better.  None of them aspires to cure liver cancer, just make money for shareholders over the last few months of the patient's life.  But I guess they have to keep cranking the arm or BigPharma will run out of cash to develop something really interesting that works. In my socialist paradise, I'd stop this unimaginative duplication of effort and make the other companies go straight back to the drawing board (by which I mean the pure science blue-skies laboratories that are no longer funded by government money) and try a completely different tack.  And I'd make everyone come up with less dorkinib and stupinib names for their products!

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