Time was, when a verdict of cancer was an instant death sentence. Today, what is gaining currency is the phrase “living with cancer”. Not just patients of breast, prostate and cervical cancer, most patients survive at least five years after the detection. According to the American Cancer Society, the survival rate is 66 percent for all cancers.
Behind this remarkable change is the continuous research in the field- the precision radiation methods, chemical and surgical methods and even a vaccine - which evolved over the last 40 years. The targeted cancer therapy, viral magic bullet and stem cell treatment are important remedical keywords now !
The biggest problem in cancer treatment is stopping the collateral damage – destruction of normal cells – which makes it difficult for the patient to survive the treatment. Direct targeting of cancer cells has thus become the holy grail of cancer research.
Targeted therapies are a direct spin-off from the mapping of the human gene, which has shown the disease in a new light. Cancer is no longer a blanket term. Tumours of no two humans are exactly the same. Result : development of drugs which target specific genes and their mutations, which, one day, can possibly lead to personalized drugs.
In contrast, viral ”magic bullets” - otherwise known as oncolytic virotherapy, may develop into a more general form of treatment that will target cancer cells anywhere and everywhere. Stem cell therapy targets tumours at their very inception and hopes to block the abnormal cell division leading to their growth.
“In targeted therapy, we zero-in on specific mutations. It is only effective for people who have those very mutations in their gene,” said Dr. Mark Chris, Chief, Thoracis Oncology Service, Memorial Sloan-Ketering Hospital, New York, who was in India recently. In Sloan Kettering, patients undergo a test in the very beginning to determine if a targeted therapy will work for them. But does this guarantee a cure? “No” said Chris. “The cancer does come back and then it needs a different drug. This means constant R & D for second and third generation drugs, but fortunately, pharmaceutical companies have been able to keep up so far”.
The breakthrough in targeted therapy came in the case of breast cancer. The first molecular target was the receptor for the female sex hormone oestrogen, which many breast cancers need for growth. Blockng the oestrogen’s binding with receptor inside cells proved an effective approach for breast cancer.
Today nearly a dozen drugs for targeted therapies have been approved by the US Food and Drug Administration. The best examples are Imatinib Mesylat ( Gleevee, which works for gastrointestinal stromal tumour and certain kinds of leukaemia); Trastuzumab ( Herceptin for certain types of breast cancer) and Dasatinib (Sprycel for Chronic Myolytic Leukemia and Acute Lymphoblastic Leukaemia).
Viruses have provided another way to tackle cancer cells without interfering with normal cells. “Viruses have thousands of years of experience in infecting cells. So it is possible to use these to target tumours.” Said Dr Kevin Murphy, Chief, Central Nervous System and Storeotactic Radiosurgery, University of California, who was in Delhi recently.
Murphy also represents Genelux - one of the many pharmaceutical companies trying to develop this particular mode of treatment. It is currently conducting the Phase II clinical trial of a virus in India along with Artemis Health Institute, Gurgaon and Sloan Kettering.
The idea of using viruses against cancer has been a perennial one. But making it harmless for normal cells and at the same time, strong enough to bypass the immune system, proved the stumbling block. At the turn of the Century, labs across the world hit upon the technique of tailoring the virus. The “Attenuated derivatives” of Adenovirus and Herpes Simplex are popular choices today.
In case of the Geneluz trial, the virus used, codenamed GL-ONC 1 is laboratory configured version of Vaccinia - the cow pox virus used as the small pox vaccine.
A part of medical fraternity, however, scoffs at such big ticket research powered by cash-rich pharmaceutical companies, which they claim, is geared towards profits and cancer incidences in the Western world.
“What is new is not always effective, or effective everywhere” said Dr Rakesh Jalali, Associate Professor of Radiation Oncology at Mumbai's Tata Memorial Hospital and the general secretary of the Indian Society of Neuro Oncology. “ A typical example is the case of mammography for breast cancer. It works in the West as patients are mostly post-menopausal women. In India, where most patients are young and have denser breast tissue, it is of little help. It gives a clean chit when there is sufficient cause for worry”. There is a need for clinical trials, but these must be done keeping the Indian situation in mind, he said.
One example is the simple, cost –effective procedure developed for breast cancer at Tata Memorial itself: a simple injection of the female sex hormone progesterone before a breast operation, which causes a 30 percent reduction in mortality.
Dr R A Badhwe, Director, Tata Memorial Hospital, who led the research, said it began in 1998, and was a fall-out of four year retrospective study he did at Guy’s Hospital, London, which indicated that surgeries occurring when the progesterone level in the body is high, were more successful. “Though injections, we created that artificial environment in the body”, he said. For the same outcome in the West, one needs a one-year treatment with Herceptin, which costs around Rs. 30 lakh.
In December 2009, the study was presented at the prestigious breast cancer symposium at San Antonio, Texas – one of the 70 papers to be read out of the 10,000 abstracts submitted.
Similar small, cost- effective breakthroughs are in the pipeline at the Cancer Institute in Chennai too. Its Director of Research, Dr. D. Rajkumar, is particularly hopeful of two the first- the development fo a marker for cervical cancer, indicating which patient will need both radiotherapy and chemotherapy – was published in BioMed last year.
“Here we go into the sphere of personalised medicine”. said Rajkumar. “Currently, for Phase IIB and IIIB patients, both processes are conducted simultaneously. For those patients who do not need chemotherapy, it means high cost and toxicity.” The researchers, he said, have identified seven genes, the presence of which is the deciding factor.
Besides, the institute has developed the dendritic cell vaccine, capable of mopping up the residual cancer cells after traditional treatment, which has already moved onto Phase II trials, said Rajkumar. Currently the vaccine is developed from the patient’s own cells, but the institute is trying to develop a common antigen, which will ensure that it can be used by more people and thus bring down the costs.
“While cost is an area of concern, the actual problem is still the side-effects ,” reminded Dr. G. K. Rath, the Chief of Rotary Cancer Hospital at Delhi’s AIIMS. Indeed, some patients seem to feel that the treatment is worse than the disease – the usual side-effects being vomiting, diarrhoea, low immunity, stomach pains and hair loss. “Women find the last traumatic and many breast cancer patients refuse traumatic and many breast cancer patients refuse treatment or fail to return after the first round,” said Rath.
This is why one of the ongoing researches at the institute involves an Ayurvedic formulation which is expected to control the side-effects. Double blind clinical trials have been on for a month in collaboration for the Central Council for Research in Ayurveda and Siddha, which developed the drug a year ago. If it works it will be significant weapon, feels Rath.
The institute is also conducting trials with a drug containing curacumin, obtained from turmeric, which has anti-cancer properties. “Still, in cancer treatment, the movement should definitely be towards using less drugs and newer techniques,” said Rath.
So given that, will oncolytic viruses or stem cell research ultimately have an edge over personalized methods like targeted therapies – given the question of continuously developing drugs to benefit small groups of patients?
“Leaving the cost aside, targeted therapies are more rationally designed and when they work, they work beautifully,” said Dr. Ashok Vaid, Chairman, Division of Medical Oncology and Hematology, Medicity, Gurgaon. “A leukaemia patient of mine has been on drug for nine years – one pill a day since 2001. This also works for elderly people for whom chemotherapy was not an option. But science has to identify that target better, for cancer has multiple pathways, which is shy it can always come back.”
