A genius? I just love studying.

Chapter 317 The Plan Has Changed; Preparations for the Experiment

Huaxia Academy of Medical Sciences, National Key Tumor Research Laboratory
Song Chaoming looked at the data from long-term animal experiments, his face ashen.

That's how cancer cells are; once drug-resistant mutations appear, there will be no miracles, and the final result will only get worse.

Their idea seemed good, but the result dealt them a heavy blow.

"What did Professor Chen say?"

Song Chaoming put down the experimental results and looked at Tang Jian.

Tang Jian also looked somewhat haggard. "Professor Chen didn't say anything, he just told us to continue observing. He seems to have gone back to his dormitory. He hasn't been to the lab for three days."

"Teacher, look at the cover article of the latest issue of Cell."

Just then, a junior brother rushed in, sweating profusely, and said...

"what happened?"

Tang Jian took the paper from his junior brother with some confusion.

Pan-cancer analysis reveals the master switch for bypass drug resistance, targeting the PKA-mTOR signaling axis.

Song Chaoming also looked over. When he saw the title of the paper, his eyebrows furrowed and he had a bad feeling.

He snatched the paper from Tang Jian's hand and began to read it with a serious expression.

Tang Jian also came up behind the teacher, looked over the teacher's shoulder, and looked at the paper on the table.

After reading the summary, Song Chaoming sighed and leaned back in his chair.

This paper from Dana-Farber Cancer Institute completely shattered his resolve. Their research had a broader scope than theirs; their team focused on non-classical pathways in specific EGFR mutants.

Dana-Farber's research spans multiple cancer types. They discovered a common, upstream master switch pathway in various cancers resistant to targeted therapy, including lung cancer, breast cancer, and colorectal cancer.

They not only discovered a new pathway, but also elucidated how this pathway acts as a central integration point, receiving signals from different mutations and coordinating multiple downstream effector pathways. One of these branches happens to contain the PKCδ pathway that their team just discovered, which drives drug resistance.

In other words, what their team discovered might be an important branch or effector in the grand picture discovered by the other side.

In this paper, they also reported preclinical data on a novel small molecule inhibitor targeting this master switch, developed in collaboration with a pharmaceutical company. The results were impressive, and the inhibitor has already entered the preparation stage for Phase I clinical trials.

Western media are currently giving this paper extensive coverage. Given the influence of cells, this paper has already caused a great stir in Western academic circles as soon as it was published. On the other hand, Song Chaoming's paper has only just entered the field of vision of a small number of Western scholars.

Song Chaoming and the others understood that if they had published their paper in Cell from the beginning, they might have gained some attention in the Western academic community due to the time advantage, or at least made their names more well-known.

But now, even if someone discovers their papers, they would consider them not very valuable, because the Dana-Farber Cancer Institute's papers already contain all of their research.

Of course, some people might find their models somewhat interesting because of their exquisite craftsmanship, but that's about it.

Despite achieving remarkable results, the outcome ultimately proved futile. This feeling left everyone in the lab feeling frustrated, with a sense of unease weighing on their chests.

[Professor Song's team's results are indeed impressive and solid; they've discovered a new pathway... However, Dana Faber's work is truly groundbreaking; they've found a master valve.]

Not only Western media, but even domestic media outlets have changed their tone, and their reporting on this matter has become...
Our work involves in-depth exploration of specific problems, but others have proposed a universal solution from a higher perspective; the gap is still significant.

[After all, we are following behind; it's already quite an achievement to keep up with international trends and produce work like this.]

These comments, like cold rain, extinguished most of the celebratory atmosphere in the laboratory.

A sense of powerlessness and frustration began to spread.

They had climbed for three long years, thinking they had reached the summit, only to find that the real giants were already looking down on them from higher clouds. Their achievements were important, but they seemed to instantly become a footnote, a case that confirmed the even greater discoveries of others.

Song Chaoming sat in his office, looking at Dana Faber's Cell paper, remaining silent for a long time.

He admitted in his heart that the other party's work was indeed more grand and profound, and he felt a deep sense of gap, which could not be easily made up by hard work. It was a comprehensive reflection of foundation, resources, teamwork and first-class insight.

Tang Jian sighed softly, his feelings somewhat complicated. If it weren't for Chen Hui, their paper might have been submitted to Cell, but without Chen Hui, they wouldn't have been able to achieve this result.

"National Day is just around the corner, how about we give everyone a holiday?"

Tang Jian looked away from the paper and suddenly said, "None of us have had a proper rest for the past three years."

Clearly, he believed that continuing the research would yield no results, and it would be better to let everyone rest, adjust their mindset and physical condition, and then set off again.

"it is good."

Song Chaoming nodded. "You should inform everyone later. Don't wait for National Day. Let's start the holiday today, and everyone can come back after National Day."

Tang Jian nodded and turned to walk out of Song Chaoming's office.

"Wait, let's inform Professor Chen about this."

Song Chaoming said to Tang Jian.

"Ah."

Tang Jian gave a soft "hmm," picked up Dana Faber's Cell paper, and walked out of the office.

The lab members received Tang Jian's notification one after another. Although they were eager for a vacation, they were not too happy when the notification arrived, because it meant that their research would probably not yield results in the short term.

Tang Jian wasn't in a good mood either, but that's just how reality is; it won't change because of human will.

After sending the notification in the group, he took his thesis and headed towards Chen Hui's dormitory.

……

"Xiao Hui, you don't look well. Did you stay up late researching again?"

Chen Hui, who had just connected to his uncle's video call in the dormitory, was questioned by Li Tianhua.

"No, it's just that the research encountered a small problem," Chen Hui quickly explained.

Li Tianhua carefully observed Chen Hui's expression through the video, confirming that Chen Hui only looked haggard and did not appear weak, which reassured him slightly. He then continued, "Don't worry, I'm doing very well now. Nobody in the neighborhood can tell I'm sick." "Don't worry, the doctor said not to resist it, but to learn to coexist with the cancer cells. I have a good mindset now. At worst, I'll just live with cancer. I'm eating well and sleeping well, and I have a long time ahead of me."

"Living with cancer cells?"

Chen Hui raised an eyebrow, and a thought flashed through his mind like lightning cleaving through the darkness.

Was our war against cancer wrong from the very beginning?

Why must we see it as an enemy and try to kill it? Why can't we... guide it? Or even... educate it?

Just like Yu the Great's flood control, it's better to dredge than to block!
This completely overturns all previous research paradigms! It's no longer a war-oriented mindset, but rather an ecological governance mindset and a systemic reset mindset!

An epiphany washed away all obstacles like a flood. Chen Hui picked up a piece of draft paper from the side and began to write furiously on it, recording the countless flashes of inspiration that emerged from his mind.

"Eh……"

Li Tianhua on the other end of the video call opened his mouth, but in the end he neither interrupted Chen Hui's research nor hung up the phone. He simply muted his microphone, afraid of disturbing Chen Hui.

Over the years, he has often watched videos that say this kind of epiphany is rare and hard to come by. Once interrupted, it may waste years or even decades. He didn't want to interrupt Chen Hui's train of thought.

Cancer cells are essentially rebellious cells that have lost their normal growth, differentiation, and death processes.

Previous solutions all involved killing these rebellious cells.

But now, Chen Hui has changed his approach. He doesn't need to kill it from the outside, but rather reprogram it from the inside, forcing these rebellious cells back to normal procedures, either differentiating into mature cells that no longer divide, or initiating normal apoptosis to end their own lives!
He thought of gene circuits in synthetic biology, cell reprogramming technology... The cutting-edge biological papers he had studied over the past six months, and various cutting-edge technologies, floated into Chen Hui's mind like starlight, as numerous as the stars in the sea.

The key is how to design an extremely precise, safe reprogramming vector that works only against cancer cells.

He immediately connected it with his previous misguided research. His understanding of all the signaling pathways in cancer cells, AI prediction models, and even the failed adaptive design all became valuable data foundations, providing incredibly accurate target maps and operating manuals for the new approach.

dong dong dong.

I had just finished organizing all my thoughts when there was a knock on the door.

"Uncle, I've just figured out a very crucial question, and I'm going to verify it now. I'll hang up now."

Chen Hui saw that the video call was still connected.

The call lasted for more than three hours, and Chen Hui's phone battery was running low.

Li Tianhua quickly turned off his phone's mute function and said with a smile, "Go ahead, go ahead."

Seeing Chen Hui make a breakthrough made him happier than if he had accomplished anything himself.

After hanging up the video call, Chen Hui opened the door and saw Tang Jian standing outside with his thesis in his hand.

"Professor Chen, I think you might need to take a look at this paper. It's an article published in *Cell* by the Dana-Farber Cancer Institute. They..."

Tang Jian told Chen Hui the heavy news with a dejected expression, his voice weak and listless. He seemed to have a sense of "why did fate create both Zhou Yu and Zhuge Liang?"

Chen Hui showed no sign of frustration. On the contrary, his eyes lit up with unprecedented excitement when he heard the words PKA-mTOR axis, main switch, and pancancer.

He eagerly took the paper from Tang Jian, went to his desk, and began to study it carefully.

"That's brilliant!" Chen Hui exclaimed, his tone filled with pure admiration and a desire to explore. "Their perspective is indeed different; they went straight to the level of systems ecology and found the pivotal node of the drug resistance network!"

Chen Hui quickly scanned the charts in the Cell paper, his brain working at lightning speed. "This explains why our previous adaptive drug model failed. It only targeted local mutations and did not take into account the existence of a more upstream, more conservative coordinating center that was directing the drug's actions from behind the scenes."

He turned to look at Tang Jian and said excitedly, "Their discovery is not our end!"

Chen Hui raised his head, his gaze intense, as if he could see into the distant future. "On the contrary, their achievements have provided the most crucial piece of the puzzle for our next step of research!"

"They found the master switch and proved that targeting it is feasible. So, what if we could design a system that not only turns it off, but also takes over and reprograms the entire drug resistance network?"

For Song Chaoming's team, Dana Faber's achievements are a towering peak that they need to look up to.

But for Chen Hui, it was an excellent springboard, a valuable signpost that validated some of his conjectures and provided a solid theoretical and target foundation for the more groundbreaking radical cure he was about to build.

What is someone else's finish line is his starting point. The cold current from the summit did not freeze his enthusiasm; instead, it became the strongest oxygen to fuel the more ambitious flame in his heart.

"This……"

Tang Jian stared in disbelief at the excited Chen Hui, and couldn't help but feel admiration.

While they were still feeling the pressure from the world's top cancer research institute, Chen Hui had already used it as a stepping stone. This kind of spirit is the attitude that scientific researchers should have.

Thinking about his earlier frustration, Tang Jian couldn't help but feel ashamed.

But is it even possible to take over and reprogram the entire drug resistance network system?

Chen Hui didn't answer him, but instead threw himself back at the computer and began frantically calculating and designing. This time, his direction was completely different.

He designed a smart viral vector based on nanotechnology, whose surface markers can accurately identify almost all lung cancer cells and the surface features shared by their mutation types, ensuring that only cancer cells are infected.

The vector does not contain poison, but rather a carefully designed synthetic gene circuit.

Once inside the cell, the program first detects the cancer-specific high-activity environment inside the cell, such as abnormally high ROS levels and specific signaling pathway activity, to perform a second confirmation and ensure that nothing goes wrong.

Once the target is identified, the program randomly initiates two branches based on the cell state, forcing the cell to undergo terminal differentiation and become harmless, no-dividing cells similar to alveolar cells or bronchial epithelial cells.

Or it can forcefully activate the cell's intrinsic apoptosis pathway, causing the cell to commit suicide.

Whether differentiation or apoptosis occurs, once the task is completed, the entire gene circuit will initiate a self-destruct program, degrading into harmless nucleotides without leaving any trace.

Cells that have been educated and die will release "eat me" signals, attracting immune cells such as macrophages to safely clear the battlefield. Differentiated cells will return to normal tissue function and may even partially repair the damage!
Tang Jian stood there, looking at the magnificent picture Chen Hui had painted, and suddenly felt that the Dana-Farber Cancer Institute's papers were like children playing house.

This idea is crazy enough, but it might actually work.

Tang Jian immediately took out his phone and posted another notice in the group, calling everyone to gather in the lab immediately. The holiday was canceled, the plans had changed, and everyone was ready to conduct the experiment!

(End of this chapter)