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Academia Sinica President Chi-huey Wong

Eyeing Cancer Research Breakthroughs


Eyeing Cancer Research Breakthroughs


Seen by many as Taiwan's next Nobel Prize candidate, Chi-huey Wong has opened new avenues in drug research. What breakthroughs does he expect to see in the next few years?

Eyeing Cancer Research Breakthroughs

By Whitney Huang
From CommonWealth Magazine (vol. 563 )

Chi-huey Wong heads Taiwan's most prestigious academic institution – Academia Sinica – but he is most recognized internationally for his pioneering research on the synthesis of complex carbohydrates and the development of new chemical and enzymatic strategies to fight cancer. In an interview with CommonWealth Magazine, Wong discusses the directions drug research might take in the future to combat cancer and other diseases that have been hard to treat. Here are excerpts from the interview in his own words (English translated from the original Chinese):

With advances in science and technology and our better understanding of genomes, the future trends in drug development will be personalization and prevention.
Every individual reacts differently to medications. So unlike traditional standardized treatments, where people with the same condition receive the same drug therapy, future treatments will place greater importance on individual differences and stress personalized therapy.

In the future, the prescription of drugs will be accompanied by related tests to identify which drugs are most appropriate for a specific patient and determine whether a particular therapy is effective.

Personalized Medicine – Testing Genes or Markers First

The most common ways to treat cancer remain conventional therapies such as chemotherapy and surgery, and they cause patients untold suffering. That can change with personalized therapies. For example, breast cancer patients can now undergo tests to see if their cancer cells test positive for the cancer-causing gene Her2  (human epidermal growth factor receptor 2). If so, you can effectively treat the condition with Herceptin, a targeted therapy for breast cancer.

Prediction No. 1: Personalized and preventive medicine will become more common.

We will also be able to take preventive action against more diseases through early detection. We can make use of markers known to be related to specific diseases to design early detection methods, which will enable detection of the disease in its early stages. Early detection means early treatment. Or, in the case of high-risk patients, we can take preventive measures to keep the disease from occurring.

Certain conditions for example have been linked to genes. In the case of Asian women who don't smoke but still get lung cancer, scientists have already identified three lung cancer susceptibility genes, offering new opportunities to prevent the onset of lung cancer among non-smokers.

Advances in imaging technology have also helped prevent disease. The integration of molecular biology and molecular imaging has emerged in recent years as the hottest field and weapon in cutting-edge biomedical research.  

Molecular imaging can be used to understand diseases. It can show, for example, how glycoproteins move from inside the cell to the cell's surface after they synthesize. If we find through molecular imaging that the glycoprotein is unable to reach the cell's surface, or has reached the surface but is structurally different from that on normal cells, that indicates the glycoproteins have a problem, giving us insight on the best way to treat the disorder. 

In terms of prevention, the new drugs or diagnostics that currently have considerable potential are concentrated on cancer and degenerative nerve diseases (such as dementia). Progress on cancer drugs is more promising, and the research priorities have been directed toward targeting at molecular and genetic markers.

When cancers form, they start with cancer stem cells that then become cancer cells before turning into tumors. Traditional imaging at present can only detect tumors, but by that time, the disease is in its later stages.

Cancer cells and cancer stem cells have specific markers, and if we can develop tests that can identify cancer cells in a patient's blood, we can treat the disease early even before imaging techniques detect a tumor.

Developing Anti-cancer Vaccines

Proteins and sugar molecules (carbohydrates) are both considered markers, but while proteins are generated by single genes, sugar molecules are generated by several genes, and they have become newly developed markers.

One of the top priorities of biomedical scientists in the past has been to find protein markers. But they had little success despite their hard work and were unable to develop vaccines. Then came the discovery of sugar molecule markers exclusively expressed on cancer cells and cancer stem cells, enabling the further development of vaccines. 

Most proteins in humans are modified through a process called glycosylation (the attachment of sugar molecules to proteins) in which the sugar molecules may be related to a disease. For example, they may affect glycoprotein folding, which may be related to neurodegenerative diseases. The progression or metastasis of cancer could also be tied to sugar molecules on glycoproteins or glycolipids.  

Prediction No. 2: Carbohydrate-based medicines will be used in cancer therapies

The medical community is currently developing a vaccine for 16 different types of cancer, including breast, lung, pancreatic, colorectal, liver, gastric, prostate, oral, brain and ovarian cancer. That's because the surfaces of the cells of these 16 cancers all have the unique glycan marker Globo H and two related types of glycolipids – SSEA3 and SSEA4.

Antibodies are also essential in combating disease. When people's bodies are invaded and infected by foreign objects such as bacteria or viruses, antibodies are the proteins produced by the body's immune system to fight them.

Human Antibodies – Limiting Immune Responses

Of the new medicines being developed today by multinational pharmaceutical companies, more than 60 percent are antibodies because developing small molecule drugs that have few side effects and can be patented has become increasingly difficult. In contrast, though the cost of developing antibody drugs is relatively high, and they can only deal with cell surface targets, the R&D process is relatively fast and they have relatively high specificity.

The development of "human antibodies" is an important trend in the use of antibodies as drugs, especially for infectious diseases, cancer or autoimmune diseases.

Prediction No. 3: The use of “human antibodies” and vaccine design will become a trend  

Human antibodies can be first identified from the B cells (cells programmed to make a specific antibody) of infected patients or even a patient recovering from the disease. The desired human antibody can then be developed through cloning and cell culture.

Take the ongoing Ebola virus outbreak. The first infection to occur outside of West Africa was a Spanish nurse who was infected after taking care of two priests with the disease. She was treated with a blood transfusion from recovered Ebola patients. 

In the past, antibodies were never made as human antibodies; they were all cultivated in rats or through the changing of some gene sequences to mirror those of human beings. But no matter what, if the antibody is not 100 percent human, its use over the long term may eventually trigger immune reactions.

Right now, the trend in antibody drugs is toward human antibodies, focusing on using people's B cells and phage display technology (a technique using viruses that infect bacteria to identify proteins) to find antibodies rather than relying on animals to cultivate them.

I've always looked forward to the day when Taiwan can develop its own human antibody technical capabilities and research vaccines at the same time.     

But the development and production of vaccines takes six months while that of antibodies only take a month, and there are no guarantees of success when it comes to developing vaccines.

Replacing Bad Genes with Good Ones

Gene therapy also has promise. Over the past three to four years, a newly developed technology called "Crispr/Cas 9" can remove bad genes and replace them with good ones. This can treat inherited diseases. 

This technology is currently making rapid advances and has reached the animal trial stage. In the future, there's a real possibility that it will be used in gene therapy and gene repair. 

In addition, the application of big data has grown increasingly important. To understand how diseases take shape, we have built a biobank that collects specimens from both healthy and sick people. Once somebody who is healthy gets sick, big data could be introduced to trace and analyze the reasons why the disease occurred and give us direction on how to prevent it. This is an important trend.

In the future, the health sector also needs to team up with information and communications technology experts to develop big data. But the problem right now is that people in the ICT field don't understand medicine and medical people don't understand ICT. People working in the two fields need to work together and be better integrated to understand and solve major disease-related problems.

Stem cell development has also made rapid advances, with plenty of room for development in the future to treat diseases that cannot be cured, such as neurodegenerative diseases and organ or tissue repair or regeneration.

Translated from the Chinese by Luke Sabatier