The c word

Welcome to the 14 new subscribers since last issue! Today, we dive into one of the most fascinating systems in the world, cancer. Also called “the emperor of all maladies”, this group of diseases is universally hated and feared. I hope after this issue you learn something new and gain a little more hope on what is in the horizon.

50% of everyone will have to deal with the c word at some point in their life.

1 in 2.

If it’s not you, chances are it’s someone you love.

So it might be hard to hear this, but I am totally awe of cancer.

Cancer cells are the most intelligent system in the entire world.

I want you to stop thinking of cancer as simply a group of cells that stops listening to healthy instructions by DNA, AKA accumulate mutations. Instead, start thinking of them as what scientist now know they are, a master manipulator.

In the process, we will uncover how their game is being exploited to diagnose cancer years before any other method.

Cancer is not a (just) about mutations.

Damage to the DNA is a hallmark of cancer, but cancer cells are only using mutations as a way to establish dominance that is far more sinister.

Cancer is a metabolic, immune, genetic, inflammatory, and vascular disease, involving several cell types all at once. In 2011, a completely new approach to seeing cancer cells was established by Hanahan and Weinberg, and research exploded into all directions to understand how a group of rogue cells often manages to take over an entire organism.

And it all starts with a home base.

Cancer cells do not act alone. They create a cult.

As they start building their manifesto of devastation, they are slowly rising, seducing and inhibiting adjacent cells to create the perfect environment to operate, this is known as the tumor microenvironment.

They inhibit immune cells like natural killer cells (which do exactly what you think they do), they create cancer stem cells, secret hormones, mimic endothelial cells on blood vessel walls, they outsmart T-cells and so much more.

But I want you to play a game of where is Wally and try to locate one of the most important things happening in the picture above.

Find the exosomes.*

Cancer cells need to be incredibly chatty in order to achieve all this. They package their messages in little parcels that can travel far and wide. But just like any good cult leader, they don’t just hand out copies of the manifesto and hope for the best. They give other cells the ammunition to start executing their plan immediately.

*Tiny little blue dots on the right bottom corner.

You probably have heard of RNA before. When cells want to copy their DNA, to express genes or to duplicate themselves they first make a quick copy in RNA.

That’s not the magical RNA.

MicroRNA and it’s founders won a Nobel Prize recently because those tiny sequences act as a maestro in the orchestra of DNA expression. miRNA can increase or decrease the expression of other genes.

I usually avoid violent analogies, but microRNA has been shown to have kamikaze-like abilities. While a gene is being expressed, they will attack messenger RNA or can destroy proteins deeming them ready for degradation. Cancer cells produce miRNA to modulate the expression of genes in other cancer cells or healthy cells. In the process, they create the perfect breeding ground for expansion, growth and immune invasion.

Most importantly, cancer cells send exosomes with microRNA from the earliest stages.

But there is a start-up that has created a way to not only intercept this mail, but to read what’s inside it.

The hero of this story is not a new therapeutic, but perhaps where we all hope every cancer story will end one day, on detection.

miSignal, was created by Japanese start-up, Craif. Founded by Ryuichi Onose, and Takao Yasui, Craif spun off from Nagoya University in Japan in 2018 with the mission to detect cancer in the earliest stages using urine.

This “pregancy-style” urine test can be taken at the comfort of your own home.

miSignal captures exosomes in urine by forcing them down microfluidic tracks. Picture tiny little tracks where fluid passes through at slow speed. The company has designed the proprietary cellulose nanowires that intercepts exosomes.

But before decoding these messages, Craif has to differentiate between friend and foe. They have designed machine learning algorithms that can detect which exosomes derive from healthy cells and which ones are potentially cancer mail. This needle in the hay stack game has been the cemetary of many good diagnostics ideas for early cancer detection. It’s extremely difficult to differentiate between normal cells and cancer cells. After all, cancer cells are not a foreign invader, they are host cells, and stealth is their craft.

At the moment, miSignal can identify and characterise those signals to determine the risk of pancreatic, colorectal, lung, stomach, esophageal, breast and ovarian cancer.

If you read this far, thank you!

Do you prefer exploring the history and future of one technology at a time, or many different startups that are trying to solve the same problem?

Let me know by clicking reply to this email

Giota