http://www.indusbusinessjournal.com/ME2/dirmod.asp?sid=&nm=&type=Publishing&mod=Publications%3A%3AArticle&mid=8F3A7027421841978F18BE895F87F791&tier=4&id=01A67CFA436A434489A10BD88C001DDALeaps and bounds in lung cancer battleNY doc leads researchers focusing on chemo drug
BY CHRIS NELSON
Dr. Shahriyour Andaz
OCEANSIDE, N.Y. – A team of physicians led by Dr. Shahriyour Andaz has uncovered breakthrough results in a pair of studies on Taxol, a type of chemotherapy drug that is often used as a treatment for lung cancer. The findings, although very preliminary, could lead to improved cancer treatments and even help determine whether a tumor is resistant to chemotherapy.
"The findings are critical to enhancing survival in lung cancer patients," Andaz, the director of thoracic oncology at South Nassau Communities Hospital on Long Island, said. "Additionally, the more concrete our understanding is of the mechanisms of cancer drug resistance, the more precise will our strategies be for cancer treatment."
Andaz’s peers in the medical community were equally impressed – the studies were among six research projects honored at the recent Murray Friedman Surgical Resident Competition. The prestigious annual event is sponsored by the Brooklyn and Long Island Chapter of the American College of Surgeons.
"We have different hospitals in this region competing for this award; every year doctors from these hospitals submit abstracts," Andaz said. "Two or three of those abstracts are selected by the competition organizers to be presented orally at a conference. To be chosen is a huge honor – it’s very humbling – and yet, there is still so much work to be done. We have a long way to go."
Andaz specializes in complex chest-cancer procedures and minimally invasive thorascopic surgery. His expertise includes chest wall sarcomas resection and reconstruction, mesothelioma, tracheal resections and reconstructions, and lung volume reduction surgery, among others.
The research team – which included physicians and study co-authors Diya Tantavi, who presented the research; Christakis Markella, Stewart Fox, Svetlana Danovich and Mary Kate Plantholt – focused on the use of gene amplification to determine Taxol resistance in early-stage lung cancer and patterns of cross-resistance in early-stage lung cancer that had already been treated.
In simplest terms, gene amplification is the production of multiple copies of a gene; it occurs naturally within a person’s body and can also be induced in the controlled environment of a laboratory. Researchers use gene amplification to produce enough copies of a selected chromosome so that the DNA may be analyzed via conventional genetic techniques. But gene amplification has also been linked to drug-resistant tumors, which are one of the most vexing problems in cancer treatment.
In the fourth edition of Cancer Principles and Practice of Oncology – widely regarded among medical professionals as the authority on cancer – Dr. Vincent T. DeVita, an internationally recognized pioneer physician in the field of oncology and currently, the chairman of the Yale Cancer Center advisory board, characterized drug resistance as "the principal cause of chemotherapy treatment failure."
Drug-resistant tumors, which can continue to grow and spread even in the presence of chemotherapy drugs, tend to have a gene known as MDR, which stands for Multiple Drug Resistance. The protein product of this gene is located in the membrane of cells and is capable of selectively ejecting molecules from the cell – including chemotherapy drugs. Why this occurs in some people and not others remains a mystery to the medical community.
"That’s what we want to figure out," Andaz said. "You see, chemotherapy is predominantly not a cure, but a treatment for cancer; sometimes it works and sometimes it doesn’t – that’s what is so frustrating to cancer researchers. What we are trying to accomplish with these studies is how to predict the target in a subset of patients where we know that it will work – we want to eliminate those patients that we know won’t respond to chemotherapy. But how do you predict this? That is the difficult part."
Andaz and his research colleagues set out to determine the effectiveness of Taxol, a generic cancer medication that interferes with the growth of cancer cells and slows their growth and spread in the body, when gene amplification is present in Chromosome 1q25. Taxol is recognized for its success in treating lung cancer and various other malignancies, including breast and ovarian cancers. Despite preclinical and clinical success of cancer drugs like Taxol, tumors developed a resistance to them in some people, rendering such treatments ineffective and presenting researchers a major obstacle in their quest to treat and cure cancer. The team employed a test known as the Extreme Drug Resistance Assay, which was developed for testing drug responses in solid tumors in the controlled environment of a laboratory, as part of the experiment. In it, they stained 40 lung tumors with Chromosome 1q25 and then screened the tumors to find the amplified regions. In 10 of the specimens where the 1q25 amplification was present in three or more of the gene copies, they proved to be extremely drug resistant to Taxol. The first study concluded that Taxol is less effective when gene amplification is present in Chromosome 1q25.
"This is not a cancer treatment," Andaz said. "What we’re trying to do is use it as a predictor of cancer treatment – whether tumors will resist drugs like Taxane. It’s important to differentiate between response and resistance, because this is not a predictor of how a tumor might respond to a treatment; it’s a predictor of the resistance to the response. The goal is to avoid giving drugs to a patient when they might not work, and avoid the unnecessary and unpleasant side effects these drugs cause."
Andaz used an EDR Assay test that was developed by Oncotech Inc., a Tustin, Calif.-based company that provides molecular oncology testing services to hospitals in the United States and Europe. According to Oncotech, its EDR Assay is the only one capable of accurately identifying extreme drug resistance in solid tumors more than 99 percent of the time. Validation of Oncotech’s EDR Assay has been documented by more than 450 clinical tests over an eight-year period – the results of which were published in the Journal of the National Cancer Institute. Follow-up studies have demonstrated a direct relationship between EDR Assay results and a patient’s survival.
In the second study, Andaz and his team examined patterns of cross-resistance to the cancer drug Cisplatinum in 82 lung cancer specimens. The specimens, which also showed resistance to five other drugs, were exposed to each drug at levels five to 80 times greater than the maximum allowable dosage for five consecutive days in a highly controlled laboratory environment. The results showed that if malignant cells are manufactured under such extreme exposure conditions, then the typical treatment would be ineffective more than 99 percent of the time.
Andaz said the evidence is compelling enough to warrant careful evaluation of the chemotherapy drugs that will be used after surgical removal of early-stage lung cancer tumors. Chemotherapy is typically given to patients after lung-cancer surgery to increase their chances of survival. Currently, most oncologists use a platinum-based chemotherapy that yields a minimum 5-percent increase in survival over five years. Platinum-based chemotherapy, which is also known as heavy-metal alkylating-like agents, has been used to treat cancer for more than three decades. The therapy works by interfering with the genetic material inside the cancer cells and prevents them from further dividing into more cancer cells.
"The results of this study will help oncologists identify the second drug that will be most effective in treating a tumor that has show to be EDR to Cisplatinum or a Cisplatinum-based chemotherapy, thereby increasing the rate of survival after nonsmall lung-cancer surgery," Andaz said. The goal of both studies is to produce enough information that could someday help doctors decide which cancer patients are unsuitable candidates for chemotherapy. "As a physician, I give my patients to oncologists for chemotherapy treatment of stage-two diseases; each one of them receives the same drug but the oncologist doesn’t know whether it will work or not," Andaz said. "The only way that you will know is if the cancer recurs; why not avoid giving a patient a drug for which the cancer cells are resistant to? Because it’s a waste of resources, and you’re wasting the patient’s life."
Andaz, 48, was born in Bombay to parents of Iranian descent. He received a bachelor’s degree in medicine and surgery in 1981 from Bombay University, a postgraduate degree in general surgery in 1985 from the College of Physicians and Surgeons in Bombay and a master of surgery degree from Bombay University in 1986. Andaz eventually left India to continue his education in the United Kingdom. In 1993, he came to the United States.