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Yearly Archives: 2019

September 18, 2019 no comments

Cellular social networks give cancer cells a cloak of invincibility

Ever since DrugBaron studied biochemistry at the end of the 1980s, one question about cancer has always perplexed him: why can we induce almost complete remission and yet the cancer can come back stronger and invariably kill the patient?  The answer now, as then, has always been selection of the rare, resistant mutant.

 

But DrugBaron was always left with a nagging doubt.  Two observations seemed to call that obvious and simple answer into question.

 

Firstly, for the most part that is not what we see with infectious agents.  Even viruses, which share with cancer cells a short generation time and a ready ability to mutate, can usually be cured as long as you hit them hard – because the chances of a resistant variant existing in the population is quite low.  As long as you don’t give them time to find one over many generations, you can eliminate the infection.  Since tumours typically have a much smaller cell population size than an infection, it follows that cancer should be easier to cure than it is.

 

Secondly, some cancers, such as some leukemias can be cured almost every time, while others, such as the brain cancer glioblastoma, are almost invariably lethal.  Yet there is no obvious association between mutation rate or the cancer cell population size and tractability of the cancer type.

 

It’s hard to put a finger on it, but it has always felt like a key part of the puzzle was missing.

 

And then, a few years ago, DrugBaron was sitting in a bar in Cambridge, UK, enjoying a drink with my friend and colleague Professor Miro Radman, when in the space of an hour he suggested to me exactly why some tumours were essentially invincible.  The missing piece, it turned out, was the ability of cells to form networks.

 

For sure, I was aware that cells often formed connections with each other.  Indeed, skeletal muscle is made up of giant syncytia formed by the complete fusion of many individual cells that give up their autonomy to work together.  In other tissues, the cells remain separate but communicate through numerous channels, such as the gap junctions between cardiac cells that ensure the contraction during a heartbeat is carefully co-ordinated.  But, like most people, DrugBaron had never considered the full implications of such cell networks before – and certainly never imagined they had anything to do with cancer.

 

Prof Radman’s concept was logical enough: if cells are highly connected, then they cannot change phenotype very easily.  Rather like a snake with two heads, if one wants to go left and the other right, it will continue down the middle.  In the same way, networks of cells ensure phenotypic stability in normal tissues.  For any cell …

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January 23, 2019 no comments

Even scale-up chemistry is not “just cooking”

Ask star antibody developer and Medicxi partner Kevin …

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March 6, 2018 no comments

Cult of Crystallography

Biological macromolecules, such as proteins and DNA, are …

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September 29, 2015 no comments

Spotting Baby Unicorns

Valuing biotech assets, whether an early-stage private investment …

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June 4, 2015 no comments

A DrugBaron Glossary

To mark the fifth anniversary of this blog, …

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May 20, 2015 comments

The perils of ignoring negative data

This week, Eleven Biotherapeutics ($EBIO) announced the failure …

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June 26, 2014 no comments

“On the way to changing the world, there are no signposts” : the illusory power of precedents

Precedents play a central role in the drug …

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April 30, 2014 no comments

Drug prices are (unnecessarily) high because R&D is (unnecessarily) inefficient

Let me put it in bold text and …

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March 3, 2014 no comments

Medicalizing biomarkers – the sure-fire road to commercial success

Creating new drugs is a process fraught with …

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January 23, 2014 no comments

Even odds-on favourites can lose: lessons from the Prosensa story

With the details from the DEMAND-III study, the …

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