Number 10 Cancer Treatment

The plan is for me to write a series of blogs about cancer. You will read this small paragraph every time you read one of these blogs because it is an explanation and a disclaimer. First of all, why should I do this and what qualifies me to do so? The answer to the second question is that I am a cancer immunologist with a PhD from the University of Pennsylvania and have 30-years experience in not only research, but also in the experiences of cancer patients. I have published numerous articles and a book about immunity to cancer and have two other books about my experiences with research and cancer patients as well as a fictional account of the final cure for the disease. However, none of this experience allows me to give advice or otherwise tell people what to do if they have cancer. I can be viewed as a participant/observer who will be relaying current and past observations about this world called “cancer”, which many people do not understand. That’s the answer to the first question, which is why I should do this. The first step in overcoming anything is to understand it first. With that being said, here they are:

Number 10 Cancer Treatment

M. Cancer treatment

The nature of cancer treatments, to a certain extent, has evolved over the last 30 years. However there are some lingering problems such as general toxicity and the use of chemotherapy as a shotgun. That last statement refers to using compounds that inhibit rapid cell growth, which includes rapidly dividing normal cell. Early treatments for cancer used chemical agents (chemotherapy) to retard the rapid growth of cancer cells. Scientists who identified the fact that cancer cells have a higher metabolism than normal cells developed these chemical treatments. Cancer cells take in more nutrients and substances at a higher rate than their normal counterparts. Scientists also found that if they administered low doses of a toxic chemical, the tumor cell would absorb more of it and die. But prolonged exposure to these chemical agents produced harmful side effects. One immediate effect of this type of chemo use is hair loss. Because the cells within hair follicles have a high metabolism these drugs target them. Despite this, their use has been successful in treating many malignant cancers. Anti-cancer drugs have a long history that go back as far as the 1930’s where Yale researchers became interested because of the effects of mustard gas in an accident. Apparently the victims of this accident were completely devoid of an immune system and had vastly lower numbers of white blood cells. The gas had eliminated the lymphatic system, which contain these rapidly dividing cells. The scientists got the idea to use an injectable form of the active compound because of a type of cancer called, lymphoma (white blood cell cancer), which at that time was deadly. These patients made a remarkable, but transient recovery.

One agent used in early treatments was called Mitomycin-C. It was a by-product of a certain type of bacterium and later made in the lab. It has the ability to cross-link the DNA chains. The cell is unable to divide because the separation of DNA is an essential component of cell division (mitosis).

In early studies, the doses were too high and sometimes led to the death of the patient. When the chemical is dissolved it displays a deep blue color. In the initial trials, it was clandestinely termed “The Blue Death” after a rat poison. Extensive clinical trials have proven that at the proper dose and rate it is effective against esophageal cancer, breast cancer, and bladder tumors. It also is used in the laboratory so that scientists (mostly tumor immunologists) can study immune T cell responses to tumor cells. Since the tumor cells cannot divide after Mitomycin-C treatment, the only measurable cell division comes from the stimulation of T cell nuclear replication and cell division induced by the inactivated tumor cells.

The evolution of Mitomycin-C from toxic chemical to a useful chemotherapeutic agent took years. Today, chemical agents used for cancer therapy are designed to attack specific tumor cell products that are unique to the tumor, which can lead to the death of only the cancer cell. This type of chemical therapy reduces the side effects normally associated with use of broad-spectrum chemical agents. Broad-spectrum agents would

often weaken or severely deplete the very cells (immune cells) in the body capable of removing the cancer cells. Broad-spectrum chemotherapeutic agents, including the ones mentioned above, are toxic to the body to one degree or another. The problem is the age of the patient. Two patients with the same cancer diagnosis but 35 years apart in age may get different modes of treatment or different doses of the same chemical. The younger

patient (say, 20 years old) can withstand a higher dose for a longer period of time than the older patient (55 years old). Therefore, the prognosis (possible outcome) of the same type of cancer can be better for a younger person. This is simple physiology, but there are exceptions and in some cases completely opposite results. This is the nature of chemotherapeutic treatment. Scientists are now recognizing that the response of a tumor to chemotherapy is related to the genetic make-up of the patient. Scientists noticed that patients with the same type of cancer who responded positively to a given agent had identical genetic markers. So, in a new approach they could design these drugs around the genetic make-up of the patient. This is an ever-changing field of scientific research, which will be joined by a newer type of cancer treatment called immunotherapy.

So what is immune-based therapy (immunotherapy) for the treatment of cancer and how did it start? This type of treatment began in the mid-1970 while scientists were studying a mouse tumor model. The tumor was blood-born and usually lethal, but they found an active immune response to the tumor. The tumor cells were grown in the lab. Once the cells were inactivated (using Mitomycin-C) they were cultured with normal mouse lymphocytes (T cells) over a series of days in a temperature and gas controlled incubator. After this culture period it was found that the T cells had become immune to the tumor with the ability to kill them. Subsequently, massive amounts of these T cells were produced. Mice were given an inoculation of small numbers of live tumor cells followed by an injection of tumor-immune T cells. Under controlled conditions it was discovered that the mice that received the immune T cells survived much longer than those that did not. This technique was called “adoptive transfer.” This ushered in an entirely new approach to treating cancer. Recent advances in genetic transfer have allowed scientist to genetically engineer T cells to make them recognize the tumor. This means that normal T cells can be removed from the body, genetically altered, and then returned to the circulation to fight the tumor. This technique is used in conjunction with natural immune-stimulating proteins such as lymphokines. This is how the natural processes of the immune system can be manipulated to fight previously lethal cancers described in a very simplistic manner.