AICR ScienceNow
Volume 30
Fall 2009

Scientist in the Spotlight: Arup Bhattacharya, PhD

For chemotherapy to do its job, the drugs first must seep out of the blood vessels and penetrate the tumor. Yet tumors develop their network of vessels rapidly. The resulting vessels, abnormal and leaky, often prevent the drug from uniformly reaching inside the tumor, leading to higher doses and harmful side effects. Selenium just may help, explains Arup B. Bhattacharya, a researcher in the Department of Cancer Prevention and Control at Roswell Park Cancer Institute. With support from AICR, Dr. Bhattacharya’s lab studies suggest that selenium may normalize irregular tumor vessels, increasing the anticancer drugs that reach the tumor and leading to a more effective treatment.

Q: Your research has focused on selenium compounds improving chemotherapy; why is getting drugs to a tumor difficult?

A: The tumors I am working with are hypoxic [able to survive with low oxygen]. What we have found is that 70 percent of all solid malignancies have regions of hypoxia and/or areas that don’t have vessels. The drug can’t get to them. There is also a difference between tumor blood vessels and normal blood vessels. In normal blood vessels, when you are short of oxygen, the vessel can expand because it is elastic or it can constrict, as required. Tumor blood vessels are like a flaccid balloon. Initially it leaks everything but the tumor is a bound region, like a capsule, and the leaked liquid leads to back pressure. In most tumors this fluid pressure is high and when it’s high, it’s not good for drug delivery. In research, you find all these beautiful drugs in a Petri dish, but if the drug doesn’t reach all the regions inside the tumor, it has minimal benefit.

Q: How do the tumors get enough oxygen and nutrients but not drugs?

A: Because basically most of the targeted drugs are bigger molecules compared to very basic nutrients and oxygen. And also, the tumor really doesn’t need too much because it is mutating all the time and is able to survive in severe conditions.

Q: What led you to work with selenium to increase drug

A: Scientists were looking at stopping tumor blood vessels from growing completely, and we were looking at this one drug to see if it can enhance chemotherapeutic efficacy. But what we found is that you can’t stop blood vessels from growing completely. There is not one factor, there are hundreds of different factors, and a tumor is smart; if you block one it will use something else to grow. Then our goal was to increase the drug getting into the tumor by 70 to 80 percent. We had started working with selenium. And we found that when the drug is used in combination therapy with selenium, it works very well.

Q: Why selenium?

A: With selenium there are several advantages. There’s a lot of research investigating selenium and cancer prevention. Selenium blocks certain master molecules these molecules regulate many other angiogenic molecules. Another advantage is that the selenium form we’re using humans can tolerate extremely well. The worse side effect is that you may get garlic breath garlic has a lot of selenium. And it’s extremely inexpensive compared to other drugs.

Q: What did your studies show?

A: When we used selenium, we gave it to the animals daily at the maximum tolerated dose starting seven days before and continuing during the full length of therapy. Then we saw a two- to four-fold increase in the drug inside many of the tumors. It significantly reduced tumor growth while normalizing the tumor vessels.

So far, we tested it on head and neck cancer and colorectal cancer. Selenium also seems to works for small cell lung cancer. We have found that this synergistic action is not tumor specific, host specific, or drug specific.

Q: What are the next steps in your research?

A: Selenium is already in clinical trials at Roswell Park partly based on our initial work. We are also following this up in New Zealand. There, the soil content of selenium is poor, so in those areas we believe the benefit could be much higher than in the United States.

Q: You worked in several different fields in India, earning a bachelor’s degree in biophysics and then moving to business. What led to the career changes?

A: When my dad moved to Bombay he was robbed and he had to start his life all over; we were not financially OK. In school, I started in the sciences, in microbiology and biophysics; then I asked my dad what he wanted me to do and he said “whatever you think.” So I jumped ship and did my management and law degree. I was working in the corporate world, in business, making good money. Then one day I was going home from work and I got really depressed, I thought, “I’m wasting my life, this is not what I really want to do.” Slowly, I shifted back into the sciences.

Q: You also practiced homeopathy?

A: Yes, homeopathy is big in India. I got a masters degree in psychology and also completed my homeopathy studies, and then I had a busy practice in India. When I came to the United States, I studied in New York with a world-famous homeopath. I still practice.

Q: Does your work in homeopathy relate to your lab research?

A: I believe that natural supplements and homeopathy have a future in medicine because there are fewer or no toxic effects compared to the drugs used in mainstream medicine today. Mainstream medicine often tries to suppress and stop the problem while homeopathy works to retain balance. When looking at lab science, you’re often just seeing a very small part of the microcosm. I generally try to have a global view of everything.

ScienceNow is a quarterly publication of the American Institute for Cancer Research.

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The American Institute for Cancer Research (AICR) is the cancer charity that fosters research on the relationship of nutrition, physical activity and weight management to cancer risk, interprets the scientific literature and educates the public about the results. It has contributed more than $96 million for innovative research conducted at universities, hospitals and research centers across the country. AICR has published two landmark reports that interpret the accumulated research in the field, and is committed to a process of continuous review. AICR also provides a wide range of educational programs to help millions of Americans learn to make dietary changes for lower cancer risk. Its award-winning New American Plate program is presented in brochures, seminars and on its website, www.aicr.org. AICR is part of the global network of charities that are dedicated to the prevention of cancer. The WCRF global network is led and unified by WCRF International, a membership association that operates as the umbrella organization for the network. The other charities in the WCRF network are World Cancer Research Fund in the UK (www.wcrf-uk.org); Wereld Kanker Onderzoek Fonds in the Netherlands (www.wcrf-nl.org); World Cancer Research Fund Hong Kong (www.wcrf-hk.org); and Fonds Mondial de Recherche contre le Cancer in France (www.fmrc.fr).