A revolution against cancer is unfolding and were just getting started – ZME Science

Posted: August 3, 2021 at 1:54 am

Its hard to put just one label on Aaron Ciechanover. He was awarded the Nobel Prize in Chemistry for characterizing the method that cells use to degrade and recycle proteins usingubiquitin, but his background stems from biology, and he was also trained as a medical doctor and a surgeon. When it comes to understanding the intricacies around human health, few people on Earth can claim the broad view that Ciechanover has.

Which is why, when he says hes excited about whats to come in medicine, its hard not to share his excitement.

The future of medicine is going to be revolutionary, Ciechanover said at the 2021 Lindau Nobel meeting, which took place online this year due to the pandemic. The meetings bring together Nobel laureates and young scientists to foster scientific exchange.

Back in the days when Ciechanover was studying medicine, he recalls, things were very different.

Lets say, if a patient had a tumor, we were not interested in the molecular mechanism that underlies the tumor development, because we did not have the tools to study it, he says.

The procedure was simplistic and straightforward. Doctors would look at the imaging facilities they had access to at the time (either X-ray, CT Scan, or MRI) and decide whether the tumor could be operated on. Surgery was generally the preferred procedure because the tumor mass could be extracted. If the tumor was too big or was touching essential organs, then doctors would try to decrease its size using chemotherapy or radiation, and then try surgery.

But these were (and still are) very harsh measures, with harsh side effects.

They are like shooting a fly with a cannon. They are not discriminating between the healthy tissue and the sick tissue, they are very difficult to direct, Ciechanover explains.

Then, at the turn of the century, a revolution started unfolding. In 2000, a landmark paper published in the journal Nature opened the floodgates of genetic discovery.

I remember it very well, this exciting day when Nature magazine came out with the first human genome. The first human genome gave us the information, the library of what we are made of. This was really the very beginning, but the last 20 years have seen enormous progress. We are now able to diagnose the disease much better [..] and we are able to analyze tumors or any other disease at the molecular level.

Heres a sense of how much things have progressed. The price of whole human genome sequencing was around $2.7 billion in 2003. Today, its under $100. Advancements in technology and decrease in price has made genetic and molecular analyses more widely available, and its not about to stop.

We are developing dedicated tools to stop the tumor or the disease at large, with a very gentle tool directing a bullet direction at the underlying mechanism, Ciechanover adds.

Even with conventional medicine, healthcare has benefited tremendously. Things like imaging, antibiotics, vaccines, operating procedures, and so on, have made a tremendous difference in how we treat patients. But now we are into a much bigger revolution, Ciechanover believes. He foresees a future where the very definition of medicine will change. Finally, we will start treating patients, not diseases, and patients will receive individualized treatments.

Tasuku Honjo is also optimistic. He believes that while cancer wont be eradicated anytime soon, theres a good chance well be able to keep most cancers in check.

Honjo should know. He and his colleagues discovered a molecule called programmed cell death protein 1 (PD-1). They also showed that this molecule functions as a sort of braking system for acquired immunity making sure that your immune system doesnt go into overdrive and cause autoimmune disease. But too much PD-1, and the immune system would not do its job properly.

For instance, several tumors produce something similar to PD-1, which helps the tumors escape the immune system. But if PD-1 could be suppressed in cancer patients, then we could use peoples own immune systems to fight cancer. This is exactly what Honjo says can help keep cancers in check.

Honjo and colleagues found that blocking PD-1 in mice can cure tumors by reactivating acquired immunity in 2002. Then, in a landmark moment in 2014, the treatment of cancer in humans by PD-1 blockade was approved by regulatory bodies in Japan and the USA. Now, there are over 1,000 clinical trials happening in the world, and PD-1 treatments seem to be effective against a wide variety of cancers, with long-lasting positive effects.

Another Nobel-winning discovery that could help our fight against cancer is CRISPR/Cas9.

CRISPR is becoming a mainstream methodology used in many cancer biology studies because of the convenience of the technique, says Jerry Li of NCIsDivision of Cancer Biology.

CRISPR is a relatively simple but very powerful and accurate way to edit genes. It was inspired by nature, from a defense mechanism some bacteria use to protect themselves against viral invasions. The bacterium captures snippets of any virus intruders DNA and stores it as segments called CRISPRs. If the same virus returns and tries to attack again, the bacterium searches its DNA library and releases an enzyme called Cas to slice up the invaders DNA.

Gene editing is not new, ProfessorEmmanuelle Charpentier, one of the pioneers behind CRISPR explained at the Lindau Nobel meeting. But thanks to the work of Charpentier and Jennifer Doudna, who were awarded the 2020 Nobel Prize, we have access to unprecedented tools.

The first CRISPR cancer therapy was launched in 2019. The goal of the study is to edit patients own immune cells to better detect and kill cancer. The treatment is safe, and early results are encouraging but CRISPR is still just getting warmed up.

This [trial] was really a proof-of-principle, feasibility, and safety thing that now opens up the whole world of CRISPR editing and other techniques of [gene] editing to hopefully make the next generation of therapies, said Edward Stadtmauer, M.D., of the University of Pennsylvania, who is involved with the research.

Weve come a long way in our fight against cancer in the past half-century, but despite improving diagnosis and treatments, theres still more work to be done if we want to keep cancer in check. But the tools we need to do so are now coming in.

With approaches like CRISPR or PD-1, researchers can develop customized, efficient treatments with few side effects. Thanks to the likes of Honjo, Charpentier, and Ciechanover, we are witnessing a new revolution of medicine, and its hard not to share their enthusiasm for whats to come.

Its still early days and there are plenty of hurdles to be overcome, but the science is progressing in leaps and bounds. It may not be today or tomorrow, but were gathering the weapons to fight cancer and its shaping up to be a big arsenal.

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A revolution against cancer is unfolding and were just getting started - ZME Science

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