Reprogramming Cancer to Self-Destruct
Stanford researchers developed a way to direct cancer cells to self-destruct.
This past week, Nature released a paper by a team of researchers from Stanford who developed a way to "rewire cancer drivers to activate apoptosis." If the only word you recognize in that sentence is "cancer," join the club. But thanks to ChatGPT, I was able to break down their research paper into normal people English and learn what I now understand to be a groundbreaking concept in cancer treatment.
Let's start by defining a few terms from that first sentence:
Cancer drivers are specific genes in our bodies that promote the growth, survival, spreading and resistance to treatment of cancer cells. So these drivers not only help cancer rapidly spread, but also give it the armor it needs to fend off the cancer treatments.
Apoptosis is a way for organisms (like the human body) to maintain the health of tissues and organs by causing unnecessary cells to self-destruct. You can think of this as biological pruning. In the same way that you would prune a plant to help it flourish, your body prunes its cells.
So if we re-write the title of that paper in normal people English, we'd get something like:
"Researchers from Stanford developed a way to direct cancer cells to self-destruct."
Of course, it's not actually that simple and research is very different from a production-ready therapy but that's the easiest way to think of it. After digging into the science for a few hours, I'm going to do my best to break it down into normal people English below. This article will be a relatively short one, so stay with me!
Let's dive in!
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The Cancer (DLBCL)
First, the researches targeted a certain type of cancer that affects the lymphatic system called Diffuse Large B Cell Lymphoma (DLBCL). For the purposes of this article, we'll just refer to it as "Lymphoma." While they tested this therapy across 906 cancer cell lines, the research proved most effective in hematopoietic and lymphoid tissues related to BCL6 expression. What's BCL6 you ask? Great question.
The Target (BCL6)
There's this protein called B-Cell Lymphoma 6 (BCL6) that plays a critical role in the development and function of B-cells. B-cells are a type of white blood cell that helps your body fight infections.
You can think of BCL6 as a Purchase Order that tell the body how many B-cells to produce. So when there's a genetic mutation in the Purchase Order (BCL6), B-cells end up getting produced in higher quantities and this unregulated B-cell growth is what we call Lymphoma.
Then there's this other protein called Bromodomain-containing Protein 4 (BRD4) which is kind of like a Manufacturing Plant. And when it binds with a high concentration of BCL6, its abnormal activity is responsible for activating genes that suppressing apoptosis which, as we now know, is the biological pruning or natural cell death that helps your body stay healthy and balanced. When apoptosis is suppressed, tumor growth goes unchecked.
Somehow, we need to target both the Purchase Order AND the Manufacturing Plant and get them both to calm down.
The Cure (TCIP)
What the researchers developed is this small molecule called a Transcriptional/Epigenetic Chemical Inducers of Proximity (TCIP). Basically it’s a combination of two molecules.
The first molecule targets high concentrations of BLC6 like a heat-seeking missile. This is what gives TCIP its specificity so it can target cancer cells but leave healthy cells alone.
The second molecule (BI3812) acts kind of like a straight jacket and it can bind itself to the rogue BRD4, disrupting gene activation and allowing apoptosis to do its thing and self-destruct.
So when you release TCIP, the heat-seeking missile molecule targets all of the cells with high BLC6 expressions (eg. Purchase Orders for too many B-cells) and the straight jacket binds itself to the BRD4 so tightly that it disrupts their ability to activate certain genes. Since it's specifically targeting cells with high BCL6 expressions and binding the BRD4, it's particularly effective in cancer cells while leaving the healthy cells alone.
The human body is an complex, beautifully designed organism with the capacity to self-regulate, adapt and heal. But we live in a broken world where things don't always work the way they were designed to. TCIPs are an early step toward correcting some of the "bugs" in our genetic code and restore our body's ability to function as it should. I'm hopeful for a future where cancer is listed alongside polio or smallpox as a tragic piece of our history, but no longer a threat to future generations.
That's the future we’re building.
That’s all for this one - I’ll catch ya next week.