Report on AACR Conference – April, 2007 – Los Angeles, CA By Nora Carbine, Advocate I was able to attend the AACR (American Association of Cancer Researchers) conference for the first time in April, 2007, as an advocate in the Scientist <-> Survivor Program. It was a great conference that was quite different from the San Antonio Breast Cancer Conference, which I have attended twice, or the SPORE workshops. First of all, although San Antonio is a pretty large conference, AACR is huge, and the facility was huge. The number of presentations and posters is absolutely overwhelming; there is no chance that you will ever be able to see and hear everything you would like. The second big difference is that the conference is for cancer researchers, so although there are some clinicians here, the vast majority of attendees are lab researchers, which casts a different light on things. Perhaps it was just because it was in LA, but things seemed more laid back, and people weren’t as formally dressed or as high-paced. There was also less discussion of using slightly-tweaked drug regimes for treatment, and naturally more basic bench research presented. The third major difference that I especially noted was the location of the exhibitors; they were located in between sections of the posters, in one block that you usually cut through to get to posters either to the left or right of the exhibitors. The poster section was a long way away from the presentations, discussions, and plenary sessions, so you really had to want to go there for a significant period of time, and they were open during most sessions. This had the effect of making the exhibitors less prominent than where they are located in San Antonio, since you didn’t have to pass them to get to all the presentations. There wasn’t quite as much mass grabbing of goodies at the exhibitor booths, and of course, lots of them were for books, videos, lab equipment, etc. so it just didn’t seem quite as flashy as at San Antonio (which I thought was good). One of the great things about attending under AACR’s auspices was the prerequisite reading material. It was extremely useful in understanding some basic research I had shied away from in the past other than in a superficial way. I felt I had a pretty good grounding in the breast cancer area as a graduate of NBCC’s Project LEAD and a past member of the Georgetown Breast SPORE, but since AACR deals with all cancers, there are some general concepts that apply to the whole field that are somewhat complicated to understand. The best “article” in the reading for me was "The Hallmarks of Cancer" by Douglas Hanahan and Robert Weinberg, published in Cell in January, 2000. It outlines the elements that the authors believe are the common features shared by all cancer cells: “…cancer cell genotypes….manifest…six essential alterations in cell physiology that collectively dictate malignant growth: self-sufficiency in growth signals, insensitivity to growth-inhibitory (antigrowth) signals, evasion of programmed cell death (apoptosis), limitless replicative potential, sustained angiogenesis, and tissue invasion and metastasis.” They go into great detail explaining the chemical and cellular processes for each of these features, and go over signaling pathways and the Integrated Circuit of the Cell (which is a quite daunting chart but really helped me understand some of the more technical research). I also enjoyed reading "Beyond Fast Tracks for Drug Approvals" by Thomas Roberts and Bruce Chabner from the New England Journal of Medicine, July 2004. I was interested to read this sentence: “Market theory suggests that sponsors will invest in the research necessary to identify subgroups of patients who are likely to have responses [to drugs] only if this process helps them to achieve approval for marketing, gives them a competitive advantage over another product, or increases their market share.” I can give anyone who is interested the entire list if you contact me. Since there were two poster sessions each day with hundreds of posters, you had to limit yourself picking which posters you wanted to see and discuss with the presenters. I decided to focus on dietary subjects and was extremely encouraged to see the number of posters in the area of “natural” products (this was an actual designated subject area). Of course, just because a substance has a “natural” origin, it doesn’t mean it’s safe or better than anything else. However, there were many interesting posters that did use natural substances, especially those derived from plants that are already consumed by many cultures, as the basis for their treatment or preventative “drugs.” Most of these were studies of substances used in vitro (in the lab with cells) or in vivo (usually using mice) and not tried in humans yet, but I find it promising that there are so many researchers concentrating on this source of cancer prevention and treatments. There were posters dealing with Triphala, an Ayurvedic herbal medicine usually used as an antioxidant made from dried and powdered fruits of three plants, here used for inhibition of pancreatic cancer cells; effects of white tea, EGCG and caffeine on tumorigenesis and b-catenin expression; and reduction of invasiveness of estrogen-negative human breast cancer cells using extracts from red grape skin, bilberry extract, or black currant extracts. There were lots of discussions of soy in the diet, coffee consumption and its effects, red wine polyphenols, and posters on Chinese and Korean medicinal herbs, cruciferous vegetables, green tea, chamomile extract, ginger and mangosteen fruit derivatives, and a number on the effects of curcumin (a spice used in curry powder) on pancreatic and breast cancer cells. The most important posters for me are discussed below. There were three posters on the subject of pomegranate fruit extract or juice from the same group at the University of Wisconsin and one poster on pomegranate extract from UCLA; it seems pomegranate is a hot topic for cancer researchers in the natural products field. The UCLA poster (Sartippour et al. abstract 2574) showed that pomegranate extract may have potential in the treatment of prostate cancer; their poster was titled “Pomegranite extract inhibits tumor angiogenesis, hypoxia inducible factor-1a, and vascular endothelial growth factor in human prostate cancer cells in vitro and in vivo.” Two of the UW posters (Zaid et al. number 2573 and Afaq et al. number 2571) dealt with use of pomegranate juice and oil for photochemoprevention using botanical antioxidants for protecting human skin against UVB damage because of its strong anti-oxidant, anti-inflammatory and anti-proliferative properties. The third poster by Khan et al. (number 2572) showed that oral consumption of pomegranate fruit extract inhibited growth and progression of primary lung tumors in mice. As the authors stated, “One way to control lung cancer is through chemopreventive intervention with agents that humans could be persuaded to consume”; a very reasonable approach, I think. They continued “An essential requirement of an ideal chemopreventive agent is that it should be nontoxic, efficacious, easily available and inexpensive. Our laboratory is defining novel chemopreventive agents that humans could consume.” This is a great approach, and as I emphasized to the presenters, healthy but high-risk people would much rather use an actual food or juice product that had been consumed for centuries without ill effects for “chemoprevention” rather than drugs that produce potentially dangerous side effects in healthy people. Other very interesting posters discussed the chemopreventive/antioxidant activity in common spices of the Apiaceae family (anise, caraway, coriander, cumin, dill and fennel) in vitro (Jeyabalan et al., University of Louisville, number 4986), seaweed as an anticarcinogenic agent in breast cancer (Teas et al., University of South Carolina, number 4988) which said that seaweed was mentioned as a treatment in the Smith Papyrus 3,000 years ago and is used in Ayurvedic medicine in India, and cloudberry extract suppressing intestinal tumorigenesis in mice and inhibition of colon carcinoma cell motility in vitro (Pajari et al., Ludwig Institute for Cancer Research, number 4984). The abstracts for all these posters are avilable from the AACR 2007 meeting site. The link below will take you to the complete collection of accepted abstracts. http://www.abstractsonline.com/viewer/browseOptions.asp?MKey=%7BE3F4019C%2D0A43%2D4514%2D8F66%2DB86DC90CD935%7D&AKey=%7B728BCE9C%2D121B%2D46B9%2DA8EE%2DDC51FDFC6C15%7D As a great add-on, medical students from a small local university came for lunch with the AACR advocates one day. Their advisor had worked with them on a poster project, also dealing with anti-cancer use of pomegranate, and they brought their poster to lunch. We had them put it up in the room with all the advocates’ posters and had them present their poster along with the advocate group, which was fun and encouraging to talk with young students hoping to work in the cancer research field. There were very few plenaries, unlike many other conferences I have attended, but the most informative presentation for me was at a plenary where Dr. Craig B. Thompson from the University of Pennsylvania in Philadelphia spoke. It was very technical, but in part because of the reading I did before the conference, it was understandable. It helped me understand the relationship between being overweight in humans and raising the risk of cancer, and builds on the concepts outlined in the Hallmarks of Cancer. He outlined how tyrosine kinase pathways evolved to regulate cellular nutrient metabolism in mammals, with glucose and amino acids of major importance for the function of cells. Enhanced fuel signaling to a cell without activation of a cell growth signal to regulate it (which would occur with increased glucose uptake) would allow the cell to become autonomous. If a cell loses apoptosis ability, it can live as if it’s running on battery power for three to four weeks, which is enough time to migrate to where can get more stimulation and can proliferate. As the cell gets more energy than it needs just to maintain itself, it damages its DNA, one of the main ways for cancer to develop. In fact, it has been observed that there is a high glycolytic rate in tumors; low glucose levels in cells inhibit proliferation, but as new pathways of biosynthesis emerge, pathways that control growth get turned off and the cells become dependent on glucose. However, there is another way cells can survive if the glucose source is limited. The P53 cell pathway is used to survive stress, such as chemotherapy. The cells then resort to autophagy, which is cannibalizing the insides of the cell in order to survive in the absence of glucose, so the cells can adapt to glucose limitation metabolically. Interestingly, type 2 diabetics on metformin, a diabetic drug, have lower rates of cancer, which suggested to Dr. Thompson that inhibitors of cell autophagy should be added to chemotherapy to keep cells from using this option to survive. There were also some Special Interest Sessions presented by AACR for participants in the Scientist <-> Survivor Program that were very informative. These were similar to the Hot Topics sessions in that they covered certain essential topics, but consisted of one speaker with lots of question and answer interaction with the listeners instead of a panel of presenters. Two of the sessions that I attended were of particular interest to me – The Tumor Microenvironment and Metastasis with Danny Welch of UAB and Epigenetics with Jean-Pierre Issa from UT MD Anderson Cancer Center. Dr. Welch said that invasion and metastasis are two different concepts – some cancers invade (go wide and deep at their site) but don’t metastasize. Different cancers have a predisposition of where they metastasize, with some tumors sending out signals before they ever spread to the rest of the body to establish a “metastatic niche.” Some tumor cells can move between basal cells and epithelial cells, not out where white blood cells can “see” them and attack, which is called perivascular spread. The cells make a nice pathway for the cancer to spread, rolling along and picking up other cells on their surfaces to act as a protective “shield” for them. They can co-opt blood vessels, kick out the normal cells and let the blood supply them instead. Then the cancer cells make a tumor-cell lined tube so the blood can flow through that (vascular mimickry). The cancer cells can then detach from the primary mass and go on to adhere to another site (dysregulated adhesion). Dr. Issa explained the difference between genetics and epigenetics. Genetics = information: Epigenetics = how and when to use that information. So epigenetics is like an add-on on top of the genetics, like something that attaches to the gene that allows it to express or not, and is influenced by its environment as with inflammation, diet, etc. Young healthy people have normal epigenetic patterns, but as we age, we acquire epigenetic changes in patches. The tissue still looks normal, but as time goes on, cancer can develop in those patches. DNA methylation (transcriptional) maps areas to use or not. Hundreds of genes are hypermethylated in each cancer, which is ten times more common than mutations. There are surprisingly few “driver” mutations in cancer, he said, perhaps ten or so. We need to think of another approach to attacking cancer, as in using drugs to restore normal gene function and stopping the hypermethylation, not trying to kill the cells but normalize them, which would potentially be less toxic than current therapies. There are a couple drugs out there now that are being tried that are actually older drugs being used again in this new way. Decitabine is one of them that affects methylation at low doses but not high doses; it takes longer to get a response and takes repeated exposures to work. This sounds to me like a good area for exploration. In conclusion, the AACR conference provides a different perspective on cancer research than that possible at other conferences in my experience and is well worth attending. I do know that the 2008 conference will be held in San Diego, so us East Coast residents have to travel a long way again. I would encourage advocates to inquire about the Scientist <-> Survivor Program, an excellent way to be introduced to this conference and be included in an informative program. Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.