Be Bopin' For the Cure

I was invited to give a talk at the Pink Out event in Harrisburg.  I asked if I needed to bring my own computer or if they were all set up.  She said "what do you need a computer for?"  PowerPoint?  So, I just realized I had agreed to give a speech, no slides, not a scientific presentation or lecture-- yikes just a talk.  They wanted me to talk about the advances in cancer care since the 1950s in keeping with the fund raising theme.  I told her I didn't do breast cancer research, but that I worked on ovarian cancer.  No problem, the entire audience will have ovaries.  So, I wrote the following speech.  I practiced at the lecturn in my office, tried it out on my lab group, and it seemed like I had dialed it in just right for the anticipated audience.  We packed flaxseed into about 200 eppendorf tubes as party favors, and the organizers put one at each place.  I went around to the vendors,introduced myself and handed out flaxseed samples.  One woman asked if it was a suppository.  Yikes!  It was quite an affair with vocal performances from music students at Southeastern Illinois College in Harrisburg.  Impressive!  Then after some more prefunctory comments, I took the microphone and delivered my spiel.  The 200 women in the audience sat quietly staring at me, with no emotion or response.  When I finished there was a brief delay, and then polite appluase.  The organizer took the mike, thank me and said "ooo, that was a lot of information!"  Too much I fear.  I guess I am not ready to hit the talk show circuit yet. 

Keynote address at Be-boppin’ for the cure 

Harrisburg, IL March 7, 2015

We are all here because in one way or another cancer has touched our lives.  To those of you who are survivors, congratulations—I wish you the best in your continued recovery.  About the worst possible news anyone can get from their doctor is the cancer diagnosis.  You know that your life and lives of your family, friends, and associates—are all now changed by the elephant in the room.  From that moment the journey begins.  For some that journey is all too short, but more and more, every day that journey continues for years, for decades, for the rest of your natural long life.  My mother died of cancer when I was 16.  Two of my sisters are breast cancer survivors, each having survived recurrent disease.  Everyone is touched by this monster.  But there is hope and the tide is turning.

Because of our nation’s investment in cancer research, more people are surviving cancer than ever before.  Today, 2 out of 3 people live at least 5 years after the cancer diagnosis.  In the 1970s, only 1 out of 2 survived that long.  The death rate has dropped nearly 20% since the 1990s—finally reversing decades of increases.  This progress reflects advances in every area of cancer care—prevention, screening, chemotherapy, surgery, radiation and increasingly molecularly targeted treatments.  These advances continue to bring new hope every day and mark a change in our thinking—we now know that the cure for cancer is prevention.  The War on Cancer, launched by President Nixon in the 1970s was a milestone in the national investment, as was the doubling of the NIH budget during President Clinton’s administration.  Another significant landmark was the sequencing of the human genome in the early 2000s and we continue to draw new insights and develop new targeted therapies from genetics—at an accelerating rate with the development of new more powerful gene sequencing technologies. 

Thinking back on previous milestones—in the 1880s William Halsted was first to usher in more aggressive surgical approaches—the radical mastectomy in which the entire breast, surrounding lymph nodes and chest muscles were removed—to prevent recurrence by removing the cancer beyond the margins.  He was quoted as saying he was “loathe to disfigure a woman” but knew he had to, to save her life.  In the 1970s more limited surgery was introduced—total mastectomy, which set the stage for more modern breast conserving surgeries such as lumpectomy. 

In 1903 after Marie Curie discovered radium, radiation therapy for solid tumors was introduced.  Radiation therapy continues to be an important tool in for the oncologist with methods of precisely targeting and delivering the radioactivity to the tumor but sparing adjacent tissues.   Radiation therapy following breast conserving surgery is highly effective in treating breast cancer.

With the introduction of the Pap test, named after George Papanicolaou, cervical cancers can be detected and removed before they have a chance to spread.  Since the 1950s, widespread use of the Pap test has helped to reduce cervical cancer rates by more than 70%.  The key to this success is early detection and effective screening strategies.  Certainly early detection for breast cancer (mammography 1970s), prostate cancer (PSA, 1986), colorectal cancer (fecal occult blood test, 1967—are key to the ever better news for these cancers.  Regular screening leads to the detection of highly treatable early cancer, and this is why the cancer statistics for these cancers have improved so dramatically—screening and effective early detection.

In 1947 chemotherapy was added to the armament of the physician—the use of nitrogen mustard, the same lethal compound used in WWI—mustard gas, was shown to effectively kill cancer cells by modifying their DNA.  Hodgkin’s lymphoma is still treated today by a modified variant of nitrogen mustard.  But as is the case with all chemotherapies—the fast growing cells are killed, usually cancer cells, but unfortunately these are deadly toxic poisons that kill normal healthy cells—and almost kill the patient in the process of delivering the cure.  In the 1950s when my mother’s cancer was discovered, she suffered through nitrogen mustard treatments.  I was too young to know what she was going through but she later told me how sick it made her.  It worked though—she lived for 15 years with her cancer.

In 1958 combination chemotherapy was introduced and has proven to highly effective in treating many cancers, especially leukemia and other cancers of the blood.  These early findings set the stage for the modern era of chemotherapy when multiple drugs at specific times and dose intervals are proving effective against many cancers. 

In the 1950s everyone smoked cigarettes, but the probable connection with lung cancer was first suggested—then in the 1960s the link to smoking was widely accepted, and today, lung cancer is still the most preventable form of cancer—prevention is the cure—quit smoking!  Asbestos, other environmental toxins are now also known to cause very specific cancers—again all curable by prevention.  Sun exposure’s link to melanoma revealed another environmental cause of cancer.

In the 1970s adjuvant chemotherapy was introduced—chemotherapy following surgery was shown to increase survival in breast cancer.  Now adjuvant chemotherapy is widely used, especially in the treatment of ovarian cancer. This has proven to be one of the most important advances—9 out of 10 women with breast cancer survive more than 5 years because of this innovation.

In the 1980s vaccines against specific cancers ushered in the age of immunotherapy.  Hepatitis B vaccination prevents a majority of liver cancers.  In 2006 vaccination against human papillomavirus (HPV) was shown to completely prevent cervical cancer. 

Chemotherapy in the modern era was ushered in with the discovery of taxanes in the early 1990s, highly effective as adjuvant therapy for breast and ovarian cancer, now available as the synthetic paclitaxel.  Taxanes were discovered as a natural product isolated from the bark of the yew tree.  The development of the synthetic assuaged fear that the natural source of the drug would be exhausted due to the demand. 

In the wake of the human genome project and with every more sophisticated understanding of cancer biology, the 21^st century heralds the era of targeted therapeutics which specifically attack the cancer without attacking the innocent bystander.  Gleevac, rutisumab, trastuzumab (Herceptin), imatanib, gefintinib, avastin--- all are “pathway specific” drugs, either immune based or activity based therapies.  Other important adjuvant therapies such as tamoxifen for estrogen sensitive breast cancers are also proving to be powerful additions to the oncologist’s toolbox. 

One of the most significant findings, which I believe heralds the new era of cancer prevention medicine, was the discovery of the link between obesity and cancer in 1998, and then the link of diabetes to cancer—leading to our understanding of the role of inflammation, obesity and diet in cancer.  The idea that diet can cause—or prevent cancer is not new.  But the actual use of “dietary intervention” for cancer therapy is still an idea that is gaining acceptance.  The concept that we can target the inflammation that causes cancer with diet is the very essence of the research in my lab. 

It has long been known that ovulation—when the egg leaves the ovary to enter the Fallopian tube—is an inflammatory event.  The ovary is wounded by when it expels the egg, and then has to heal—a classic inflammatory event.  Repeated rounds of this tear and repair cycle, every month year after year creates a ripe environment for the cancer to start.  It’s been said the cancer is the wound that will not heal.  There is a very strong link between the number of ovulations and ovarian cancer.  The best way to prevent the disease is to limit ovulations—multiple pregnancies, breast feeding, contraceptives are all protective against the disease.  The more ovulations, the more inflammation and rounds of wound healing.  We had a simple goal, find natural product antioxidants that we can use to target the inflammation in hopes we could attack the disease.   

One of the reasons that so little progress has been made in ovarian cancer is because there are very few adequate animal models for studying the disease.  Rodents do not get ovarian cancer unless you cause them to get it, either by manipulating them genetically, or by causing it with chemicals or drugs.  These are useful models for studying therapies for late disease, but can’t help us understand what causes the disease—because the investigator has to induce the cancer.  Amazingly, chickens are the only animal that gets the same kind of ovarian cancer that women get, and importantly they are afflicted with the cancer spontaneously—so we can study old, cancer prone hens which have ovulated every day for over 2 years, and study the earliest stages of ovarian cancer, to help us find a way to prevent it from starting and also to develop tests for early detection.  Prevention and early detection are both seriously lacking in the treatment of ovarian cancer. 

There is a lot of public interest in omega-3 fats—fish oil is known to be cardioprotective and potent anti-inflammatories.  We were considering how to give chickens fish oil, to give them omega-3 fats, when I discovered “omega eggs” in the dairy case at the health food store.  Wow, I thought, if the chickens accumulate omega-3 in the eggs, the ovary has to see it too.  How do they get all that omega 3 into eggs?? They feed the chickens flaxseed!  I thought that surely there must be a lot known about the health benefits of feeding hens flaxseed, after all the omega egg business represents about 15% of the shell eggs sold in Canada, and about 3 % in the USA.  Nothing was known about flax effects on hens.  All that the large scale egg producers care about are the eggs, not the chickens.  So we decided to see if we fed hens flaxseed if it might not have some beneficial effects and maybe even prevent or reduce ovarian cancer.  We conducted a series of studies to fine tune the feeding and analysis, and then embarked on a one year study where we fed 400 chickens 10% flaxseed for one year.  The diet had profound effects.  The flax fed hens looked better, maintained the same lean body weight throughout the study, far fewer of them died—their overall wellbeing was much improved by the diet.  But the important finding was that the severity of the disease was significantly reduced by the diet.  There was a 70% reduction in the severity of the cancer, the hens that did get cancer presented with early stage disease.  This exciting finding indicated that flaxseed reduced the inflammation that drives the cancer, and causes it to slow to the point that the cancer was no longer lethal to the hens! 

These exciting findings enable us to attract substantial funding from the NIH to conduct more studies on how the flaxseed works to treat the disease.  These studies are ongoing in my laboratory at the SIU School of Medicine in Carbondale.  We are finding some very exciting things, including possibly identifying a potential biomarker to help detect early disease, and we are just now starting a clinical trial to test the effectiveness of flaxseed in women who are in remission after initial surgery and chemotherapy for ovarian cancer.

The use of taxane and platinum based therapy post-surgery (i.e. adjuvant therapy) has proven to be highly successfully in the initial treatment of ovarian cancer but the standard of care and outcomes for ovarian cancer have not significantly improved for the last four decades.  The initial round of therapy is successful and provides on average two years of disease free living—but in some 75% of women the disease returns, and the recurrent disease, again treated with combinations of chemotherapeutics with good success—but eventually in the majority of cases, the disease will return, and now be resistant to chemotherapy, and the woman will ultimately succumb to the cancer.  We have just started a new clinical trial for women who are in remission post initial therapy to try and prevent the disease from returning.  Instead of just waiting, we are giving these women a daily dose of flaxseed, 20 grams a day, every day in hopes that this simple dietary supplement will keep the disease at bay.  Based on the success of our trials in the cancer prone hens, where the flax significantly reduced the progression of the cancer, we are hopefully that this intervention will prove to be effective for women.  Our goal is to turn ovarian cancer into a disease women can live with instead of die from.  Talk to me if you know someone who would like to enroll in this trial.