Fighting the war against cancer
Posted: Wednesday, June 1, 2011 8:01 pm
Biologic research, during the past four decades, has clarified the molecular structure and the genetics of the cell. The cell as we know, is, the basic building block of all tissues. The study of molecular biology and genetics give us a road map of how the normal cell, is transformed into a cancerous one. This process is known as carcinogenesis.
Laboratory studies involving animals proved that chemicals such as tar, can initiate carcinogenesis and the continued exposure to these, over a period of time, leads to the development of cancer .
Similarly it has been proved by statistical studies, that, cigarette smoking and the consequent exposure, of the lung tissue to tar containing products in smoke, is linked to more than 85% of lung cancers. Even after the cessation of the habit, the changes initiated in the lung tissue, are retained for many years. It is now accepted that the development of cancer is principally a multi- step process which can be divided into: Initiation, Promotion and Progression.
The initial step is an event known as Mutation, which is an error in the structure of the chromosome (which carries our genetic structure) that occurs, during cell division. This error can follow the damage of cellular structure, caused by chemicals and other agents. In fact we now know that many such genetic changes occur before cells lose their identity, of function or structure.
Changes become cumulative, as exposure to the carcinogen continues and other factors allow the progress of this process. These are known as Promoters. Additionally, the immune system is progressively depressed, thereby, depleting the body’s ability to reverse these changes. The tumor cells grow rapidly, while robbing the tissue of its nutrition and gain the ability to invade and to establish colonies of cells, outside their immediate environs. This is the stage of metastasis, when the cancer has progressed to an advanced stage.
While scientific studies have elucidated the pathways of carcinogenesis and the progression of tumors, more recently, an international collaborative effort completed the mapping of the ‘Human genome’. This provides the tools, to further elaborate, molecular pathways and the genetic control of cellular regeneration.
Molecular biology also allows us to understand, the key elements of cell to cell communication. It is believed that there are more than twenty ‘tumor suppressor genes’, only a few of which have been described today. Studies have also shown, that there can be multiple and distinct differences, in cancers that affect the same tissues. For example Thyroid cancer occurs as at least three distinct cell types and each of them is associated with a different set of genes.
An important body of work that has elaborated the mechanisms of tumor initiation and growth has come from the study of viruses and their relationship to human cancers. The study of the progression from benign tumors, to cancers, has allowed scientists to map the molecular mechanisms behind these changes. The study of the Human Papilloma Virus (HPV) and the hepatitis B and C viruses have paved the way to landmark breakthroughs in cancer prevention with the development of vaccines. Such strategies in prevention are known as primary prevention, when a specific cancer causing agent can be blocked.
For more than two decades, the principal modes of treatment such as surgery, chemotherapy and radiation, used in tandem, or in a sequential manner, has become the standard of therapy in the treatment of a number of cancers. This is what is meant by the term ‘multi-modality therapy’. Biological agents derived from the serum of the patient with cancer, or a clone of immune cells, have been variously tried as also gene therapy. These have had limited success. It has now become clear that as cancers, progress, they accumulate genetic changes that are reflected in various ‘clones’ of cells within the same tumor; so that one method of treatment, fails to suppress or kill all of the cells.
And so, we have moved through a retinue of therapies, only to understand, that cancer cells have the capability to adapt and to overcome the ‘bullets’ we shoot at them. More recently the concept of ‘targeted therapies’ has come into vogue. A biological agent (Imatinib) which inhibits a key enzyme in certain leukemic cells, and has been successful in effecting a cure, has also been found to be effective, in a specific cancer that affects the gastrointestinal tract, known by a short form as ‘GIST’. But, targeted therapy when dealing with many of the cancers, because of the genetic variability of cancer cells meets with limited success.
The significant progress that we have made, however, is reflected, in our ever increasing armamentarium of tools and approaches to treatment. IMRT (Image modulated Radiation Therapy) that allows the rays to be focused onto the area involved by cancer, thereby sparing surrounding tissue and vital organs has become standard. The concepts of minimally invasive surgery for diagnosis of cancers such as Stereotactic biopsy for breast and neurologic tumors have reduced the morbidity or side effects of these procedures. Laparoscopy and image guided techniques are being increasingly used as is Robotic surgery.
While technology and newer medicines can help us to increase the survival of cancer patients, we have found that the best strategies that translate into effective ‘Cancer Control’ are early detection and prevention. Smoking cessation will effectively reduce the incidence of lung cancer. Sadly, during the last 50 years the numbers of men and women that smoke have increased worldwide. Consequently lung cancer is the most prevalent cancer in men. If the trend continues, women will soon have an equal claim to this disease. It has also been established now for more than two decades, that early detection of Breast cancer is possible, through mammography and breast self-examination. As a result of such practices, we now detect cancers at an earlier stage, when cure is possible and also detect precancerous, pathology that can be effectively treated, to prevent the development of breast cancer. Likewise screening colonoscopies can detect colon cancer in its early stages. By removing polyps in the colon, the progression to cancer can be prevented. Equally important is to follow the recommendations for PAP smears in women.
As our understanding of Genetics and cancer progresses, we will also be able to take advantage of genetic screening, for a variety of cancers. We now know that there are families in which a cluster of cancers such as ovarian, colorectal, breast and uterine cancers occur. Screening individual members of such families is recommended. Genetic screening is also available for women with strong family history of breast cancer.
We are therefore, in a position today, to use multiple strategies for cancer control. And so, while the ‘Magic Bullet’, is no longer in our current vocabulary; the War against cancer continues, as Science points us in new directions, that will take us further in our understanding of the disease, and life itself.
Dr. Rebeiro is a general and oncologic surgeon with many years of academic and clinical practice experience. He is a Fellow of the American College of Surgeons and The Society of Surgical Oncology.