Chapter 119: The Royal Swedish Academy of Sciences (6)

The hyperprogression of cancer cells

Young-Joon read the message window. Hyperprogression was a phenomenon where the progression of cancer increased explosively and the tumor grew multiple times its size in an instant.

Excuse me for a moment, Young-Joon said to Kakeguni and stepped out into the hall.

As he walked he talked to Rosaline.

Turn on Synchronization Mode. How does this side effect work?

Oh, wait. Lets see this in Simulation Mode, not Synchronization Mode.

The thing we used last time when we found anthrax?

Yes.

Dont we use that to see how a virus spreads in the country?

You can do that if you use a lot of fitness. If you use a little, you can select an imaginary person, administer any drug you want, and test it. It seems perfect for a situation like this.

Alright. Lets try it.

[Simulation Mode]

Click.

𝑓𝘳𝑒𝑒𝓌𝘦𝘣𝘯ℴ𝑣𝘦𝑙.𝘤𝑜𝑚

Young-Joon pressed the button.

Ack!

He felt a piercing pain break out in his head. His vision turned pitch black.

What is this? Rosaline?

He couldnt see anything. Jamie Anderson, who was in front of him, and Kakeguni all disappeared. He felt like he had just dropped out of the lecture and into space. The desks, computers, and chairs disappeared, and the floor turned pitch black. His feet werent even on the ground.

What is this?

Bleep!

A message window appeared in front of his eyes again.

Enter the subjects biological characteristics. [Expand]

Biological characteristics?

Chromosome 1

Chromosome 2

Chromosome 3

Chromosome X

Chromosome Y

Humans had forty-four autosomal chromosomes and two sex chromosomes. Half of them were from the father, and half of them were from the mother, resulting in twenty-two autosomal chromosomes of the same type. They were numbered by their order.

Young-Joon clicked on chromosome 1.

Coding genes

Noncoding genes

Pseudogene

The chromosome was full of coding genes, noncoding genes that controlled the expression of genes, and junk DNA that did not do anything.

Does this mean I can select all of them?

Wait Is this

Young-Joon froze up a little. He thought that he had been through most of the surprises as he worked with Rosaline, but he never imagined anything like this. This was the future technology that he ultimately wanted to implement in reality based on the Genome Project of one hundred million people and DNA analysis technology. Young-Joon, although he was the only one, easily surpassed the process, which would have taken years, through Rosaline.

Ive gotten to the final stage in personalized medicine.

Young-Joons heart thumped. He pressed on the button for coding genes.

AADACL3: Arylacetamide deacetylase-like 3.

AADACL4: Arylacetamide deacetylase-like 4.

ACAADM: acyl-Coenzyme A dehydrogenase, C-4 to C-12 straight chain.

...

They were all gene names. A whopping two thousand sixty-four genes appeared one after another. They were all the genes that existed on chromosome 1.

Holy shit, what is all this

Honestly, how could anyone know this? No one could know this, not even biologists. Even if someone worked for the Weather Network, it would be impossible for them to know the humidity of a small hill in the valley of a limestone cave located in Singi-myeon, Sancheok-si, Gangwon-do. This was the same thing.

Young-Joon pressed the first gene that appeared.

[ATGGCG]

The DNA sequence of the AADACL3 gene showed up. Young-Joon was able to manipulate the sequence as he liked. His shock had exceeded its limit.

Is this real? Rosaline, are you insane?

Dont be so touched. This isnt that difficult for me.

Still, this is

Young-Joon was able to edit all one billion letters of DNA. Rosaline could not only figure out the humidity of a small hill in the valley of a limestone cave, she could set it to whatever she wanted; she could set the hills humidity to twenty percent and make a pond twenty-eight degrees. She could basically manipulate the weather in that amount of detail.

That is an interesting metaphor. Quickly finish the details so that you can observe when and where a hurricane disappears when it occurs at a certain point in the Pacific Ocean.

This simulation was able to understand the human body mechanically. All the secrets of biology were answered.

But when will I finish setting up all twenty thousand genes?

Young-Joon pressed the [Close] button beside the message and closed all the detailed setting options.

Set it to a random patient type who can experience side effects when using the immune checkpoint inhibitor.

Sure.

Suddenly, a random, fictional patient appeared in front of his eyes. He was a pretty old man with a medium build. He had a bushy beard, and he looked Hispanic.

Beep!

His profile popped up on the message window.

Age: 63. Male.

Height: 184.5 cm.

Weight: 105 kg.

Blood Type: A

A bunch of data related to the patients lesion showed up below, and the last entry displayed the progression level of his cancer.

Lung cancer: stage 3.

EGFR mutation driven.

EGFR?

EGFR referred to the epithelial growth factor receptor. This cell divided and proliferated upon stimulation, but some unlucky cells had their EGFRs broken. These mutated EGFR would send division and proliferation signals to the cell even in the absence of external stimulation. Then, the cell would keep dividing, get bigger, puff up, and escape their designated location.

Young-Joon understood the problem right away.

The immune checkpoint inhibitor is related to the EGFR?

Yes. Administer the immune checkpoint inhibitor to this fictional patient.

Bleep!

A graphic of an antibody, which was the immune checkpoint inhibitor. Young-Joon dragged that with his finger and laid it on top of the patient.

[Routes of Administration]

Injection

Oral administration

Patch

The immune checkpoint inhibitor is an injection.

Click.

When Young-Joon pressed the [Injection] button, questions about whether it was going to be injected into the tumor or intravenously, how much should be injected, and how often it should be administered poured out.

Damn it

There were too many choices.

I dont even go to Subway because I hate having so many questions.

Young-Joon selected the intravenous injection, and chose to administer one hundred twenty-five milligrams per square meter every hour; square meter referred to the surface area of the body, which was determined by height and weight.

[Activate Simulation Mode]

At last, a message appeared. Young-Joon monitored the fictional patient nervously. The molecular phenomena appeared in front of his eyes. The immune checkpoint inhibitor that was injected intravenously quickly spread throughout the body and became concentrated in the liver.

Suddenly, dozens of genes were expressed in liver cells. The urea cycle quickly began to circulate as the genes that were involved in protein breakdown became activated. The proteinase stuck onto the immune checkpoint inhibitor and was trying to break it. A part of it broke, but a significant portion of the antibody survived and kept flowing in the blood vessels. And

Its going into the lung cancer.

Young-Joons jaw slowly dropped. The immune checkpoint inhibitor absorbed into the tumor and began coordinating the battle between the immune cells and cancer cells.

[Time: 1 day]

[Level of cancer cell death: 3%]

A new message window appeared. The time was increasing by the day every second. In proportion, the cancer cell death value was also rising rapidly. And after some time

[Time: 5 days]

Bleep!

[Hyperprogression has occurred.]

As the stop signal that the cancer cell was sending to immune cells was blocked, the EGFR popped up on the surface of the cancer cells as a complementary mechanism. As the number of EGFRs increased, extreme pressure to proliferate was being applied onto the tumor. In just a few hours, the cells began doubling. Then

[Angiogenesis has occurred.]

New blood vessels were created in the tumor.

[Time: 7 days.]

The tumor had grown more than five times larger than before the inhibitor was administered.

[The lung cancer cells have begun metastasizing.]

[Time: 10 days]

[The cancer has metastasized to the breast tissue.]

[Time: 14 days]

[The patient has died.]

[Simulation over.]

Leave

Young-Joon ended Simulation Mode.

* * *

It may be dangerous to use the immune checkpoint inhibitor in cancer patients with tumors due to mutations in EGFR, said Young-Joon.

This was the judges midterm evaluation discussion meeting. All the professors looked at him in confusion.

What are you talking about? Jamie Anderson asked.

Its exactly as you heard. It has side effects, or its actually counterproductive. EGFR is amplified on the surface of cancer cells as a complementary effect when the immune checkpoint signal is inhibited. If you use an inhibitor, the countereffect due to EGFR amplification becomes stronger than the efficacy from the immune cells from the fourth day. The proliferation of cancer cells exceeds the destruction efficiency. Thats when hyperprogression begins. The cancer cells explode in number, and the patient could die within a few days. EGFR mutations are quite common in cancer cells, so hyperprogression like this will occur in more than ten percent of patients if you use the drug in this state.

...

The table was filled with silence.

Doctor Ryu, are you being serious? Do you have evidence? Did you test this? Jamie Anderson asked.

There is no experimental data, but its a theoretical prediction.

Dont talk so carelessly if you dont have experimental data. The immune checkpoint inhibitor is a product that has already been commercializ

Professor Hariot, said Young-Joon while looking at the chairman of the Nobel Committee at the Karolinska Institute. Please let me borrow a lab.

A lab?

Yes.

Are you going to do experiments here? Hariot asked in surprise.

I will show you this with a mice experiment. Please sell me ten mice.

But those mice are not EGFR mutants, and they dont have cancer.

I can make it.

... Even if you are that talented, Mr. Ryu, can you do an animal experiment of that scale alone?

It can be done alone, but I am not alone.

Pardon?

The greatest dream team in the scientific community is here right now. The people I brought from A-Bio and Lab One at A-Gen.

...

After some thought, Hariot said, I will lend you a lab. And I will give you the authority to use all the facilities and equipment at the Karolinska Institute. How much time do you need?

About two weeks. Thank you, Young-Joon replied.

Young-Joon, who left the room after the meeting, took out his phone. He sent out an email to the top scientists who were in Sweden right now through the company messenger.

[I have started a project at the Karolinska Institute. I am looking for scientists who can stay for an extra two weeks and help my experiment. You will be given first author in this paper, which will be published in

Science

, PTO[1] equivalent to the number of days used in the study, and the equivalent of a months pay.]

Bleep!

Park Dong-Hyun, who received a notification for the email, was shocked when he saw his phone.

Wow. Did you see this? Is this real?

Cheon Ji-Myung chuckled while reading the email like he was baffled.

I knew that he was going to start a project to destroy a cancer when we go back, but I didnt know that he would start it here.

Maybe he has an allergy to taking time off?

Our CEO?

If its not that, how can anyone come all the way to Sweden and borrow someone elses lab to do an experiment?

Hehe I guess the research topic was so fascinating that he couldnt resist starting it until he returned to Korea.

But the benefits are amazing, arent they? Youre working for two weeks and getting a months pay.

Yeah. It might be really competitive. Where is the CEO right now? Cheon Ji-Myung asked.

1. Acronym for Personal Time Off.