Address At The Inauguration Of The International Symposium On Translational Research: Apoptosis And Cancer

Cancer Treatment: Challenges

I am indeed delighted to participate in the Inauguration of the International Symposium on Translational Research: Apoptosis and Cancer organized by the Rajiv Gandhi Centre for Bio-Technology, Kerala University and the MD Anderson Cancer Centre, Texas. I greet the organizers, distinguished doctors, bio-technologists, oncologists, pharmacologists and other participants in the conference.

I have been studying the work done by various institutions in the country during the past five decades. Pioneering work has been done in the area of tobacco induced oral cancer. Our researchers have been able to identify the radiosensitive action of Bleomycin, which has been used to treat oral cancer patients in conjunction with chemotherapy. This has resulted in high percentage of successes in treating oral cancer cases. With the increase in cancer cases particularly among women, where the cervical cancer alone contributes to hundred thousand new cases detected every year there is a need to find advanced and innovative ways of treating the patient. In that respect the translational research which is also known as a bench to bed concept is of vital need for treating and bringing the cancer patient to normalcy with speed. This symposium on Translational Research: Apoptosis and Cancer is definitely a timely event.

Insights into Life

I would like to share a few experiences of people and their pain and possible solution. Last year I was at the Centre for Cellular & Molecular Biology at Hyderabad. I met hundreds of young scientists working on the genetic origin and manifestation of diseases, particularly Cancer. The young scholars very enthusiastically shared with me their knowledge of molecular biology and cellular research. They told me about the information encrypted on the DNA of a cell and how both problems and solutions to the human lives reside on the software that nature has embedded in each life it creates. In a way, these young minds were dealing with the questions that were so far confined in the domain of sages and philosophers.

Cancer, unlike many other diseases that come from the external factors, like infections, life styles and other environmental and physiological stressors, emanate from within the cell. The life software embedded in the DNA material gets mutated and start growing in a way that is not in-line with the cells around. Life turns against itself. The tragedy becomes unfathomable when it happens too early.

I understand that the US Researchers have launched a pilot project to find all genetic changes that cause cancer and expect that it can open a whole new world of cancer therapy. They hope to lay the ground work for replicating the successes of a few targeted cancer therapies such as ?Herceptin? useful against one type of breast cancer and ?Gleevec? a drug that revolutionised treatment of chronic myeloid leukaemia Scientists know that cancer is a genetic disease caused by mutations or other changes in the DNA of cells. But no one has done a systematic analysis of all the mutations in various tumours. I think this Symposium must discuss and come out with a recommendation how India can become a partner in such studies which can definitely bring a new regime for detection and cure of cancer.

Sometime back, I met one gentleman whose 6-year-old grand child was on periodic blood transfusion for Thallesemia. The permanent solution, doctors told me was a bone marrow transplant. The bone marrow of the child was not matching even between siblings and the parents. Unmatched bone marrow transplant is not done in India, I was told, and even in the West it is done experimentally. I met the child who is unaware of the time bomb that is ticking inside him. I prayed for him, for this was the only thing I could do. Today, standing before this gathering of cancer experts, I think I must share with you my concern for these and other patients who live under the shadow of uncertain life. What can we do to strengthen the doctors? capabilities in such a situation? In India, we have limited beds for B.M.T. This has to be increased in multiple hospitals and also concentrate on Stem Cell research which is the live source for bone marrow production. Also when the medical community finds that a person has cancer, in addition to treating him, he should also provide him psychological support. This support should be in the form of giving him an advice to live a normal life. Now I am reminded of three of my friends who are facing this disease bravely and contributing to the society.

Brave Hearts

I have three friends so valiantly handling their blood cancers. The first one is an industrialist, second one is an author and the third one is a painter, all three are handling their blood cancers with courage. Undaunted by the presence of a disease of poor morbidity in their bodies they are relentlessly pursuing life. The industrialist says, like a gladiator, he will defeat his cancerous cells. The author is learning more about Self by writing books of great spiritual and literary value. One of his work is titled ?Celebration of the Cells?. I have invited the painter to stay in the Rashtrapati Bhavan. He created beautiful paintings capturing the beauty and life in Mughal Garden. He showed me one painting which he did while undergoing chemotherapy at the Tata Memorial Hospital. The indomitable spirit was shining over the trauma of pain. I learnt from interaction with these three men that the life of a cancer patient is a process of adjustment to a disease that at times is in remission and at other times active. Any illness or even discomfort can direct us to the often-ignored self. It can even become a journey of faith. The medical practitioners can take a lead from this experience while advising patients.

Stem Cell Research

Newer knowledge emerging out of research on stem cells from abroad and India has to be taken note of and studied. In fact, regenerative medicine is fast getting established as a complete branch of medical science. The embryo starts out as a mass of undifferentiated cells, which then divide, multiply and go down differential paths to take the shape of various tissues and organs of the body. The mechanisms which constitute this orderly process of differentiation is fast getting understood at the laboratory level. And the state-of-the-art in this area holds the promise of regenerating tissue that malfunctions due to injury, age, disease or genetic abnormality. Whether large volumes of cells can be produced from stem cells is yet to be seen. I hope that the day is not far when the similar six year old boy I met, will get a tailor-made bone marrow out of stem cells to survive for the next sixty years and beyond. The Symposium can discuss and encourage research in this area for promoting enhanced probability of success in cancer treatment.

Breast Cancer: a new project

The suffering of cancer does not remain confined to the patient alone. It often engulfs the entire family and the social surroundings. The emotional trauma is just intense. The Bangalore Cancer Research Foundation conducted a unique multi-institutional study with DRDO with the participation of Defence Institute of Psychological Research (DIPR), Defence Institute of Physiology and Allied Sciences (DIPAS) and Centre for Cellular and Molecular Biology (CCMB). The study was aimed at establishing the relationship of the stress of breast cancer patients with the neuro-endocrine response leading to immune modulation, which will determine the prognosis to treatment or progression of the disease. The perceived stress of the patients will be influenced by the social support being provided by the spouses and caregivers and hence in the study a systems approach was made to evaluate the stress of the patients in the social ambience. Patients of breast cancer, their spouses and equal number of the care givers served as volunteers for the study.

Standard psychological methods were used to quantify the stress of the patients, their coping strategies, blood cortisol, cell mediated immunity and humoral immunity were measured in all the three groups. The study revealed specific correlation of the stress of the patients with the immune responses. Patients who received adequate social support had lower level of perceived stress and their prognosis to surgical, radiation and chemotherapy were better than those who had higher level of perceived stress due to inadequate emotional support from the spouses and care givers. The primary message, which emanated from the study, indicates that for successful prognosis, it will be essential to combine psychotherapy along with the conventional medical management of cancer. It also emphasises the necessity to address the problem at the mind-body complex where the etiological factor may have the root. The sample size is small. Elaborate further research in this area is very vital.

Study on Cervical Cancer

The application of indigenous technology to make healthcare affordable as well as accessible has brought me together to Prof. Kakarla Subba Rao. We worked together on many projects that will be useful for rural people. In one such project of Society for Biomedical Technology (SBMT) of DRDO (Defence Research & Development Organisation) named TULASI, mass screening of cervical cancer was undertaken by the Nizam?s Institute of Medical Sciences (NIMS) and Deccan College of Medical sciences (DCMS). More than 50 camps in tribal and rural areas as well as in the urban slums have been conducted to screen women for cervical cancer at their door-step. Prof. M R Raju, through his Mahatma Gandhi Memorial Medical Trust, has also done some good work in Bhimavaram. A number of factors have emerged leading to cervical cancer. Early marriage, multiple childbirths and lack of reproductive hygiene, generally prevalent in lower socio-economic groups have been shown to be associated with increased risk of cervical cancer. The study also established the positive effect of use barrier methods of contraception in protecting the females against human papilloma virus. Although, TULASI Project has succeeded in creating awareness about this most prevalent of female cancers in India, an effective follow-up and treatment system to treat cervical cancer patients has yet to be established. The symposium can debate how Translational Research can help coping with cervical cancer in India.

Affordable & Accessible Therapeutics

Treatment of cancer involves any one but most often a combination of radiation, chemotherapy and surgery. Genetic diagnosis can help to take good decisions while charting the course of therapy. On the drug side, instead of looking for agents that kill dividing cells, researchers are now looking for agents that encourage cell to get destroyed. Inside a growing ball of cancer cells, the blood supply can run short, so the cells begin to suffocate. Malignant cancers get over this problem by sending out a signal to the body to grow new arteries into the tumour. These arteries characteristically grow like a crab-claw that first gave cancer its Greek name. Many drugs, called angiogenic agents, are now available to destroy these supply lines. These drugs are imported and are very expensive. Industry-hospital-research institution consortia need to be established to develop affordable indigenous products, especially using nano-technology. I understand some of our scientists have found by examination of homeopathic drugs which is used for treating arthritis, through electron microscope that it contains gold in nano-form. There is a need to carry this study further and bring medicines in nano form for delivering to the cancer patients. This may become not only a cost-effective solution since the quantity needed will be very small, but also penetrate and reach the spot precisely and cure the patient faster.

Optimisation of Chemotherapy

Chemotherapy often destroys healthy cells together with the intended cancerous ones. A firm in Pune has developed algorithms describing interaction between normal cells, malignant cells and nutrients. The algorithms also take into account the pharmaco-kinetics of the drug. Together with inputs on patient?s age, height and weight and the type and volume of the tumour, the mathematical model can design an optimal drug schedule minimising side effects. The type and volume of tumour can be automatically deduced from the CT or MRI scans. This is a good example of how advances in many disciplines of science such as Biomedical engineering, Image processing, control systems, mathematical modelling and pharmacology are helping in the development of better and effective treatment for cancer patients. This will be definitely of interest to translational researchers.

Clinical database Network

Clinical networking is an important area where certain progress has been made. A Clinical database can help in refining clinical features, documenting response to treatment and bringing out geographical or genetic variations. Increasing numbers of hospitals are using computers. However, feeding in the clinical inputs into the network requires recording of detailed symptoms through a checklist of clinical signs. Physicians are needed to think in a structured format and still not lose social and emotional contact with the patient.

Application of Clinical data base network in cancer has been attempted by Indo-American Cancer Institute at Hyderabad. Some other institutions in certain other areas may have similar databases. The database links text to images, process and protocols. They are attempting a seamless fusion of text and images along with communication among patients, their doctors, and other service providers. This can be suitably adapted for clinical data of cancer and can be developed into a Cancer Database Network. I am told that the regional cancer registry can be extended to provide this database. Two advantages are immediately apparent. Firstly pattern recognition is improved. With a large database covering more number of subjects than an individual or even an institution can expect to study, a networked database improves pattern recognition. Secondly, statistically significant evidence can be generated and validated with other Institutions in the country and abroad. Intensive practice of clinical medicine would improve on both these counts. This aspect can be discussed in the Symposium since many cancer hospitals and research institutions are participating.

Networking of institutions

There are number of hospitals providing cancer treatment in the country. It will be useful to network these cancer treatment centers for enabling consultancy among specialists and directing the patients to the right type of specialists who may be available in one of the networked institutions. This type of consultations among experts will generate confidence among medical community to undertake treatment of complex cancer cases and enable them to cure the disease with cumulative experience. Also, it will be useful to have monthly or bi-monthly conferences among the specialists of different centers to discuss the special cases treated during that period. This will create treatment synergy between centers. During one of my visits I found that cancer centers have immunologists, physiologists and psychologists working together. This model could also be followed by other centers to provide psychological support to the patients which will facilitate faster recovery.

Awareness

Patient?s own vigilance and clinician?s alertness are the primary ways in detecting early onset of cancer. Today, histo-pathological and Fine Needle Asparation (FNA) examination are most important tests to tell us about the nature of the cancer, and its aggressiveness. Recent advances in laboratory medicine like Fluorescent Activated Cell Sorting (FACS), Polymerase Chain Reaction (PCR), Fluorescent in-situ hybridisation (FISH) can be employed for more refined diagnosis. A wide variety of tools are involved in these tests. The costs are high and certain non-commercial investments need to be mobilised to make them available in more and more hospitals. The tumors are best diagnosed by contrast CT, spiral CT and MRI. More sophisticated MR Spectroscopy, Positron Emission Tomography (PET) have come in. Image transmission between multiple hospitals and Tele-medicine connected mobile laboratories, linking multiple hospitals in districts hold a great promise.

Conclusion

Translational Research has drawn increasing attention world over. In this discipline basic sciences are used to discover and characterise newer therapeutics for diseases. With this approach we can understand the mechanism why a cell should commit suicide and this understanding can be applied to a particular patient for hastening this process. Some viruses associated with cancers use tricks to prevent apoptosis of the cells. I am sure translational research may be able to find a solution to counter these tricks created by the virus. This discipline of translational research can also be applied to agriculture where experience of the lab can be taken to the land which can lead to increasing the productivity of crops and development of high potency medicinal plants. I would suggest the experts assembled here to consider the application of translational research to agriculture, improving the environment in addition to finding a solution to the treatment of cancer. With these words I inaugurate the Symposium on Translational Research: Apoptosis and Cancer. My best wishes to all the participants for fruitful deliberations on finding faster removal of pain of the cancer patients.

May God bless you.