prepared for

Summer Institute

July 22nd - 25th, 2002

Johns Hopkins Medical School Campus

by

Arthur Renkwitz

Douglas Becker

Women who used oral contraceptives, or the birth control pill have less of a chance of getting ovarian cancer. Also, women who have had several pregnancies are less likely to get ovarian cancer.

*Women who never took the pill are 2 times as likely to get ovarian cancer as those who took the pill for more than 10 years.

*The more children a woman has had, the less likely she is to get the disease.

from the National Ovarian Cancer Association of Canada-10 Things Every Woman Should Know

If you have just completed the Evolution and Cancer Quest then the above quote should sound familiar. This description of ovarian tissue turning cancerous after being exposed to large amounts of estrogen is the same scenario that accounted for breast cancer, and both of these scenarios are currently in the medical news. The fact that post-pubescent women can experience long periods of time when they are not pregnant or breast feeding is the result of recent behavorial changes. In general terms, before the advent of birth control, pregnancies and breast feeding began earlier in the lives of women. This being the case, pregnancy and breast feeding appear to be selective processes that protect the ovarian and mastoid tissues from a constant bathing in estrogenic hormones and the possibility of developing cancer.

It appears that one of the risk factors in ovarian cancer is the result of altering a cycle with evolved safety measures. Though these constant ovulations are only one of the conditions identified as causes of ovarian cancer, it indicates an evolutionary link. The "incessant ovulation" is the result of pregnancies put off, or occurring later in the life of women, and pregnancy and breast feeding are physical conditions that confer a selective advantage against cancer.

The preceding description is an evolutionary perspective on the cause of ovarian and breast cancer. It represents a portion of the evolutionary journey of humans and selective agents. The previous Cancer Quests, A Primer of Evolutionary Medicine and Evolution and Cancer, featured the explanations for this point of view and offered support through papers and interactive activities.

This Cancer Quest, Evolution and Ovarian Cancer, is an activity with two objectives in mind. The first is to familiarize you with the etiology of cancer of the ovary. The second is to explain chemotherapy as a modality for treating the cancer and how recurrence of the disease is a result of selective agents and evolution. Meeting these two objectives is tantamount to being able to use a simulation that models the growth of a malignant ovarian tumor.The goal of these objectives and the simulator is to virtually treat a tumor model with chemotherapy to see if we can determine what effect this clinical modality will have on the course of the disease.

Let us begin this Quest by completing the Evolution and Ovarian Cancer Worksheet. This will give us the background we need to interact with the simulator that will follow in the next portion of Cancer Quest.

 Because ovarian cancer is ordinarily detected in its late stages, most patients develop resistance to chemotherapy drugs. Virtually all cancers contain cells resistant to chemotherapy, and the number of drug-resistant cells increases exponentially as a tumor expands in size. After treatment is completed, the surviving drug-resistant cells often proliferate rapidly. As a result, only 25 percent of women with Stage III and IV ovarian cancer survive five years after their diagnosis.

Biological Profile

Despite its well documented biological activity, very little interest was shown in taxol until scientists at the Albert Einstein Medical College reported that its mode of action was totally unique. Until this finding in 1980, it was believed that the cytotoxic properties of taxol were due to its ability to destabilise microtubules, which are important structures involved in cell division (mitosis). In fact, taxol was found to induce the assembly of tubulin into microtubules, and more importantly, that the drug actually stabilises them to the extent that mitosis is disrupted. Such a novel mode of action was be lieved to make taxol a prototype for a new class of anticancer drugs.

The relatively non-toxic properties of taxol have made it a leading light in the treatment of cancer in the 1990s, providing a non-intrusive alternative to the more radical techniques of radiotherapy and surgery. The cost of producing sufficient quantities of this new wonderdrug, however, is a severely limiting factor. Synthetic organic chemistry may provide a solution to this problem in the years to come.-Molecule of the Month:Taxol

Carboplatin (KAR-boe-pla-tin) belongs to the group of medicines known as alkylating agents. It is used to treat cancer of the ovaries. It may also be used to treat other kinds of cancer, as determined by your doctor.

Carboplatin interferes with the growth of cancer cells, which eventually are destroyed. Since the growth of normal body cells may also be affected by carboplatin, other effects also will occur. Some of these may be serious and must be reported to your doctor. Other effects may not be serious but may cause concern. Some effects may not occur until months or years after the medicine is used.-Medline PLUS

will annihilate most of the tumor cells, but at the same time select for cells that will be resistant to treatment and lead to the recurrence of the tumor. What does this process mean to an oncologist who is seeking an effective cure for this aggressive disease?

The fact that cells produce genetic variability as they move through their replication cycles means that affecting a cure of an evolving tumor should be possible the earlier the tumor is treated. Getting to the primary cancer cells before they develop these variability factors would mean that the chemotherapy agents could destroy the primary tumor cells and a cure could be affected.

If the tumor is not discovered until later stages, then the cells are diverse enough in their genetic variability to survive the chemotherapeutic agent and affect a recurrence. Multiple drugs administered together can produce a synergism, or work individually, to create an environment where a cell might be resistant to one of the two drugs, but it succumbs to the activity of both. 

With the completion of Evolution and Ovarian Cancer you have gained the knowledge of the evolutionary etiology of ovarian cancer and the theory behind the chemotherapy modality. Now it's time to continue your Evolutionary Cancer Quest by attempting to affect a cure, or remission, of a simulated ovarian tumor by applying this knowledge in a Ovarian Cancer Tumor Simulation.

Related Links:

Evolutionary Biology Resources

This is a list of cyber resources from the Internet that deal with interesting issues in Evolutionary Biology. They were assembled to provide supplemental materials for a course in Evolutionary Biology at Saint Anselm College.

What is Darwinian Medicine?

A brief overview of: Why We Get Sick: The New Science of Darwinian Medicine by Randolph Nesse and George Williams, Vintage Books, 1996.

Darwinian Evolutionary Medicine

An editorial from the Southern Medical Journal on Darwinian (Evolutionary) Medicine

Review of Evolutionary Medicine

Lisa Sattenspiel, PhD. defines the field of evolutionary medicine as she reviews the book Evolutionary Medicine, in the Journal of the American Medical Association.

Darwinian Medicine Website

This Website was first created for Science Week 1997, after which it has continued to be devoted to Darwinian Medicine; under constant review and open to your ideas and comments.

Evolution and the Origin of Diseases

A Scientific American article explaining that the principles of evolution by natural selection are finally beginning to inform medicine

Paul Ewald:Infectious Disease and the Evolution of Virulence

The transcript of an interview with Paul Ewald on the PBS Evolution site.

Infectious Disease as an Evolutionary Paradigm

Joshua Lederberg, Sackler Foundation Scholar, Rockefeller University, New York, New York, USA

The basic principles of genetics and evolution apply equally to human hosts and to emerging infections, in which foodborne outbreaks play an important and growing role. However, we are dealing with a very complicated coevolutionary process in which infectious agent outcomes range from mutual annihilation to mutual integration and resynthesis of a new species. In our race against microbial evolution, new molecular biology tools will help us study the past; education and a global public health perspective will help us deal better with the future.

A New Germ Theory

The dictates of evolution virtually demand that the causes of some of humanity's chronic and most baffling "noninfectious" illnesses will turn out to be pathogens -- that is the radical view of a prominent evolutionary biologist, Paul Ewald.

Deadly Evolution

Deadly Evolution is an audio file from Sound Print produced by Loretta Williams and Marjorie Centofanti.

A flu suddenly becomes deadly and kills more than 20 million people. Malaria, once easily treated, has become one of the most persistent diseases of our time. Even new viruses such as HIV exhibit variations in the virus's ability to kill. A variety of factors influence the spread and deadliness of disease, but some biologists think a critical influence has been overlooked--evolution. Producers Marjorie Centofanti and Loretta Williams explore the evolution theories that could lead to change in the treatment of infectious disease.

Learn more about the scientists featured in this program: Allen Herre shares a summary of an article on his virulence research, Paul Ewald contributes excerpts from his bibliography, and Phyllis Kanki describes her experiences as an HIV/AIDS researcher in Senegal.

What You Need to Know About Cancer

National Magazine Award winning issue of the Scientific American

The Genetics of Cancer

The Genetics of Cancer is a resource center designed to help you understand the genetic basis of cancer and interpret new discoveries in the field of cancer genetics. Here you will find both clinical and basic information on cancer, heredity, and the roles that genes can play in the development of various cancers. You can search for a specific topic, step page by page through the material by clicking the "next" button at the bottom of the screen, or just see where the hyperlinks-and your curiosity-take you.

Ovarian Cancer Perspective

 Cells that stimulate the growth of cancer are most vulnerable to chemotherapy early in the course of the disease. This site has the information on ovarian tumor growth and chemotherapeutic treatment. This data will be used to describe and explain the tumor model that will be used in the third presentation in this series.

Glida's Club Worldwide

 The essential emotional and social needs of those living with cancer have driven rapid Gilda's Club expansion in the last five years. Gilda's Club Worldwide, the headquarters organization, works with communities around the world to start and sustain Gilda's Clubs and advocate for the importance of emotional and social support for anyone touched by cancer.

"Quote Me On It..."by Gilda Radner

I wanted a perfect ending. Now I've learned, the hard way, that some poems don't rhyme, and some stories don't have a clear beginning, middle, and end. A poem by Gilda Radner