AACR Scientist<-->Survivor Post #6 New on the Horizon

Most chemotherapies up until recently “poisoned” all rapidly growing cells in the body, both cancerous and non-cancerous. That’s why hair loss, nausea, vomiting, diarrhea, anemia and low white blood cell counts are commonly associated with chemotherapy. The side effects are caused by damage to normal cells that also grow rapidly like those in the digestive system and blood and hair cells.

New therapies for cancer treatment that are undergoing investigation by researchers include:

Molecular Targeted Therapies: Cancer cells grow and divide uncontrollably, develop a blood supply, and metastasize due to abnormal signals they receive inside the cell from proteins or enzymes. In cancer the normal protein and enzyme signaling pathways that regulate growth do not work properly because of genetic mutations in the cell.

An analogy often used is that of a car with the gas pedal stuck to the floor, the cells don’t stop growing and dividing when they should, the signal to grow is stuck in the “on” position and the protective mechanisms, the “airbags” and “antilock brakes” aren’t working. New research is directed to targeting abnormal protein and enzyme signaling pathways that cause cells to become cancerous. Different cancers have different signaling pathways based on different gene mutations, so the targets are different for different types of cancer.

An example of a targeted molecular therapy is the drug Gleevec. Gleevec targets a specific abnormal protein in cells of the cancer chronic myeloid leukemia. This cancer is caused by a defect in the Philadelphia chromosome, a genetic abnormality that causes the production of a cancer-causing protein molecule called BCR-ABL. Gleevec blocks this cancer-causing protein. Gleevec is taken in pill form and has few side effects, it does not involve receiving IV chemo through a port for hours in an office setting.

When Gleevec was being tested in an early clinical trial, the drug was only being tested to see if it was toxic to humans, not if it worked on the leukemia yet. But in the study, once a dose of 300mg was reached, all 31 of the 31 patients involved in the trial went into remission from their cancer. In a later study, 54 patients who had become resistant to all other forms of treatment for this leukemia were given Gleevec, and 53 responded. 5 year survival for those with this type of leukemia who are treated with Gleevec is now 95%. Prior to Gleevec, 30-50% of patients with this leukemia reached the advanced and often terminal stage of this disease in 3-5 years.

Some targeted therapies may be effective in more than one cancer if another cancer has a similar genetic mutation. Gleevec is also an example of this. Another cancer, a stomach cancer called GIST that had few treatment options but has responded well to Gleevec also.

Many other similar “targeted therapies” are currently under study and being developed. They have the potential to revolutionize cancer treatment.

Metastasis: 90% of cancer deaths are related to metastasis. If a cancerous tumors didn’t metastasize, in many cases cancer could be an easy disease to treat. Most of us with appendix cancer have been asked by someone in the general public “Well, can’t they just remove your appendix?”. For most of us that is almost never the answer, because appendix cancer has almost always metastasized into our abdomens by the time it is discovered. The metastasis is what has the potential to kill us, not usually the original tumor on the appendix. Some of the most fascinating lectures I listened to were those discussing molecular targeted therapies to prevent metastasis. Cancer that couldn’t metastasize would be a benign disease in many cases.

microRNA: micro RNAs are tiny segments of RNA that have just recently been discovered. Unlike other RNA segments in a cell that help transcribe proteins, these RNA segments function to turn genes “on” and “off”. In many cancer cells, mutated genes inappropriately turn “on” to manufacture proteins or enzymes that cause the cancer cells to grow out of control or to metastasize. Sometimes protective genes are wrongly turned “off”. Harnessing the power of microRNa could allow us to turn abnormal cancer genes “off” or protective genes that are not working “on”.

p53 Pathways: The p53 gene is the “guardian gene” in preventing cancer. It also functions through protein signaling pathways that initiate repair of abnormal mutations in a gene, or initiates the destruction of a mutated cell that cannot be repaired. In some cases when the P53 gene itself is mutated or does not function, molecular targeted therapies are being developed to enhance or correct the function and molecular pathways of a mutated P53 gene. Over 50% of those with cancer have a mutation of the p53 gene.

Biomarkers: in these studies, blood tests are being developed to identify cancers before symptoms or other tests can identify them. The goal is for these tests to be 100% accurate. Cancers caught in early stages are the most curable. Colon cancer caught early is 90% curable, but even in it’s early stage, there is an identifiably tumor. Biomarkers could allow cancers to be identified before tumors are even present so that progression can be stopped before the disease has a chance to cause harm. The goal is for the development of biomarkers that are 100% accurate.

Cancer Genomics and Personalized Cancer Therapies: In some cancer therapy, the majority of patients with a specific cancer respond to particular chemotherapies and medicines, while for others, the therapy has no effect. This is often related to subtle differences in the particular genetic mutations in an individual’s tumor. One scientist said even every breast cancer tumor is genetically different from another.

Personalized genomic cancer therapies in the future may involve genetic testing of a persons individual tumor when a biopsy is done, and identification of the particular genetic abnormalities in their own tumor. This would identify which specific targeted therapies would be effective for their particular cancer. This would prevent a patient from receiving and paying for a cancer therapy that would not be effective on their particular tumor and would allow the patient to receive the most effective treatment for their disease.

Chemoprevention: This could involve medications taken to prevent cancer in highly susceptible individuals. Currently some drugs like Tamoxifen are used to prevent recurrence in those with diagnosed breast cancer, but drugs could be developed to prevent cancer in those who have been identified to have abnormal genes that make them highly likely to develop the disease. I know a woman who’s family had a genetic predisposition to breast cancer. All of her female family members had died of breast cancer, so she had both of her breasts removed to prevent the disease in her own body. Chemoprevention may allow someone like her to take a targeted medication to prevent the disease without such radical prevention.

I’m sorry this post is so long, but I learned so much about so many avenues being pursued in cancer research at the AACR meeting. It was amazing. I have one last post to add to my series about my AACR involvement, rest your eyes in the meantime!

AACR Annual Meeting #5: What I learned about cancer

I learned so much about cancer at the AACR annual meeting. I attended many lectures by many scientists. These are some of the things I learned about cancer:

1. Some say that cancer is genetic, that the genes you are born with determine if you will one day get cancer. The truth is that the number of cancers inherited from parents is very small, though some of us inherit especially effective genes for preventing or suppressing cancer (the people who smoke forever and never get cancer). Usually cancer results from genes that become abnormal or mutated as we age, often in response to environmental factors like cigarette smoke or exposure to carcinogens in our environment. Usually cancer results from a combination of many genetic mutations, not a single mutation.

2. Cancerous mutations occur over a long period of time. Normally cancerous changes take at least 10-30 years to develop, one scientist said they may take even 30-50 years. Because of this, most cancers occur in older people. This is why cancers that occur before the age of 45, like mine, are suspected to have an inherited genetic component. With the aging of the baby boomers, the number of cancer cases in the US will increase by 30-50% as we approach the year 2020. One in three in the US will one day receive a cancer diagnosis.

3. Normally when a mutation causes cells to become abnormal, the cell has genes that automatically repair the abnormality or the cell is genetically programmed to commit suicide (apoptosis)to prevent the abnormality from being passed on. Tumor suppressor genes we normally have regulate this protection from cancer. In cancer some of these tumor suppressor genes are themselves mutated.

4. Normally cells are programmed to stop reproducing when there are sufficient numbers for the body’s needs or when they come into contact with other cells. For instance, if you scrape your skin new cells grow to replace the damaged skin, but once there are enough cells to replace the damaged skin, cells have a mechanism to signal them to stop growing. Cancerous cells have lost the mechanism that signals them to stop growing, therefore they continue to grow into masses, or tumors.

5. Normally cells only grow in their own environment and cells of one organ do not travel to other organs, and if they do, they automatically die when they are in the “wrong place”. Cancer cells have learned several methods of travel that allow them to go to other places in the body, and when they reach a new destination, their abnormal growth is unstoppable. The name for this is metastasis. Metastatic tumors are usually genetically different from the primary tumor they originated from. 90% of deaths from cancer are caused by metastasis.

6. If you remember in the news, the Human Genome Project was completed in 2003. It took 13 years, but new technology allowed the identification of the 20,000-25,000 genes in the human DNA and the identification of the 3 billion chemical base pairs that make up human DNA. This identification of the normal human DNA has allowed researchers to identify genes that are abnormal and that can cause cancer. A project is now in place, the Cancer Genome Project, to identify the abnormalities in the genes of cancerous tumors.

7. One gene discovered, P53, creates a protein that regulates cell division and prevents tumor formation, it also signals a cell to repair abnormal DNA. P53 has been nicknamed the “guardian” of normal cell genes. In one inherited genetic syndrome in which P53 is abnormal, cancer is usually diagnosed at a young age and the person is often diagnosed with multiple different kinds of cancer in a lifetime. I’ve met one woman my age who has been diagnosed with 5 different kinds of cancer in her lifetime, her first cancer diagnosis was breast cancer at age 13. I wonder if she may have had that syndrome. The P53 gene is mutated or damaged in 50-55% of people diagnosed with cancer.

8. Cancer cells are able to continue to grow into tumors and to metastasize because they are able to produce a substance that causes new blood vessels to form (angiogenisis) to supply blood, therefore food and oxygen, to the tumors. Normally this process doesn’t occur in humans except prior to birth when the circulatory system is developing, in the lining of the uterus during menstruation, or during repair of injured tissues.

9. One lecture I attended attributed 30% of cancers to cigarette smoking, not just lung cancer, but also cancers of the mouth, throat and bladder. Cigarette smoking is also related to the incidence of colon, kidney and pancreatic cancers.

10. Twenty percent of cancers are related to obesity, especially in post menopausal women. This is associated with the fact that fat cells produce estrogen. Estrogen levels in postmenopausal women are 50 to 100 percent higher among women who are overweight than in women who are of normal weight. It is also thought that a higher production of insulin or insulin-related growth factors may play a part in promoting cancer in those who are overweight. There is more information here: National Cancer Institute Fact Sheet: Obesity and Cancer.

12. Metabolic syndrome is now seen as a cancer risk factor.

13. Poor diet is responsible for 25% of cancer cases. In one study, colon cancer patients on a Western diet had 3 1/2 times higher cancer recurrence after treatment than those on an Asian diet. While not yet identified, it is believed that there are chemical agents in fruits and vegetables that protect against cancer.

14.Some infectious diseases are also associated with a cancer risk; for example HPV and cervical cancer and H. pylori and gastric cancer. Over-exposure to sunlight is related to skin cancer.

Everything I learned helped me to understand that cancer is not a simple disease. Cancer actually comprises a set of 200 different diseases. Each type cancer is different, there is no easy one-size-fits-all solution. Cancer cells have evolved from a combination of many alterations in a normal cell over a long period of time, and cancer cells have found many ways to overcome and survive the body’s normal defense mechanisms. Cancer is a vicious enemy.

I know this was a long post, so I will divide up posts. My next post will be about advances made in cancer treatment and what is new on the horizon.

AACR Scientist<-> Survivor Program #4

I lucked out on my flight to the meeting but had some trouble getting back last night. The “windy city” was living up to it’s name, so flights into O’Hare were delayed. The late flight made me miss my 7PM shuttle bus to Indiana, and I wasn’t able to catch another bus until after 11PM, so I got home about 1:30AM unstead of 9PM. But it all worked out!

I know many of you are anxious to know what I learned at the AACR meeting. I attended many, many hours of presentations and was exposed to many new ideas and concepts. I want to go through all of my notes and organize my thoughts before I present what I learned here, though. I’m working the next few days so won’t have a chance right away, but as soon as I get time to compile the information I will post it here.

In the meantime, another appendix cancer patient encouraged me to watch this video forum offered on PBS, it was great and I want to share the link here: Take One Step: A Conversation About Cancer with Linda Ellerbee . It would also be an excellent presentation for friends and family members of those diagnosed with cancer to watch.

I also received this from MSKCC today, information about emotional and social support needs of cancer patients with a video clip from Dr. Jimmie Holland: Quality Cancer Care Must Address Emotional Needs

AACR Annual Meeting #3: A Scientist and a Survivor

I am writing this while in the San Diego airport. I arrived the recommended two hours early and got through security quickly, so had some time. I stopped at the TCYB stand to get a frozen yogurt and took a seat to eat my cone. Another woman bought her food and then sat next to me. She asked if I had just attended the AACR meeting. I don’t know why she asked, as I wasn’t carrying the tote or anything that would have identified my participation. It turned out she had also attended the meeting.

Once I said I had attended, we struck up a conversation about the frustration of wanting to attend simultaneous presentations and having to pick and choose. We talked of what we’d liked about the meeting. We talked about the CD, available Podcasts, research abstracts. We got to talking further, and it turned out she was a scientist; an oncologist who had done extensive research into gastrointestinal cancers and was currently studying prostate cancer. I told her I was a gastrointestinal cancer survivor. We had an immediate connection.

I told her my cancer story and she told me of her husband, a more recent cancer survivor. We talked about her research and my survival. We talked about people we’d both known who had not survived the disease, young people who had much to live for. It was a wonderful conversation, in just minutes she felt like an old friend. I was inspired by her research; she was inspired by my survival. We were both almost in tears at one point. Before we parted, I thanked her for her dedication to cancer research; she thanked me for being a survivor, for being an example of research success. We exchanged information and plan to keep in touch via email.

Before the meeting I’d never spoken with anyone involved in cancer research. I’d probably have been intimidated by such a conversation. Having been in an environment attended by so many scientists for several days, though, and having interacted with them has really changed the equation for me.

When I heard of the Scientist-Survivor program, I wasn’t really sure I understood the philosophy. Now I feel I understand it on a more personal level. Maybe my airport interaction was a great illustration that scientists and survivors need to support, inspire and learn from each other, that we truly need to interact. Maybe in the end, our mutual passion and support will bring us that much closer to the goal of removing the terrible threat that cancer is to humanity.

AACR Scientist<-> Survivor Program Post #2 : Dr. Jimmy Holland

It will take me several entries to say all I have to say about my time at the AACR Annual meeting. It’s been an amazing experience. I haven’t seen much of San Diego as I’ve been in the conference center almost all of my time here, but I did take a short walk along the seaport after attending my last presentation today. I leave tomorrow morning to return to Chicago.

I am participating in the AACR meeting as part of their Scientist<-->Survivor program. The goal of the program is for those of us who advocate for cancer patients to be exposed to and to learn more about the ongoing science of cancer research from the scientists. It is then hoped that we will communicate our new knowledge and use it to better advocate for those afflicted with cancer.

In this post, I’d like to tell you about one especially wonderful event. On my website I list under recommended reading the book “The Human Side of Cancer: Living with Hope, Coping with Uncertainty” by Jimmie C. Holland, M.D. and Sheldon Lewis. I loved the book. I read it when I was dealing with the emotional aftermath of cancer, it is still on my bookshelf. I’ve linked an online chapter of her book to my website and blog, The Tyranny of Positive Thinking .

Intrigued by the book, I’d learned more of Dr. Jimmie Holland years ago. It turned out she’d created the field of psycho-oncology. She is a leader in addressing the emotional and social aspects of a cancer diagnosis. She is also the founding president of the American Society of Psychosocial Oncology. This is a link to her biography: Dr. Holland’s Biography . She even works at Memorial Sloan Kettering in New York City, where I was treated.

When I got here, I heard Dr. Jimmie Holland would be at the AACR meeting, she would even be involved with the Scientist<-->Survivor program! She was to give a presentation entitled “Cancer Care for the Whole Patient: Meeting Psychosocial Health Needs”. The chance to meet Dr. Jimmie Holland for me was like a kid getting to meet his baseball hero.

I was able to attend Dr. Holland’s presentation, and I was even able to meet with her personally! We talked a few times, she was very approachable and interesting. She has a help line she may allow me to post to my blog and web site. She said she would support me in giving me information and tools to hopefully start an emotional support system at a large oncology practice near my home. She is a very caring doctor who truly sees the whole cancer patient. When we talked, she said 50% of those diagnosed with severe cancers like ours seek professional emotional help at some point in time. I’m sure an even greater number of us could benefit from that. In hindsight I wish I had sought help during the first several years after my diagnosis. It might have made that time a little easier.

But I think it’s imperative that our oncologists and medical professionals learn to address us in a more holistic way. I remember reading my chart once (I always do that). The only part of my oncology chart that ever addressed the emotional aspect of my diagnosis was an entry in a physician progress note that documented I was a bit emotional during my initial appointment (the one where I was told I was not likely to survive to raise my kids, who were 10 and 11 at the time). No other reference was ever made to anything other than my physical exams at future ongoing appointments.

I hope one of the things I take home from this meeting is an abilitiy and inspiration to help others in their emotional cancer stuggles at the large oncology practice where I was treated.