Cancer and AIDS: A Symbiotic Relationship

AIDS has commandeered media headlines, instigated public awareness, and garnered funding in more profound ways than any other disease in history. Bolstered by a tenacious activist community, HIV/AIDS research has blazed trails empirically, politically, and even philosophically. Since this disease took hold some 15 years ago, new insights and understanding in immunology, cytokine biology, antiviral research, vaccine development, and gene therapy have emerged from HIV/AIDS research laboratories and crossed over to cancer research. The relationship between AIDS and cancer is, of course, symbiotic. While HIV/AIDS research is now benefiting cancer research in numerous ways, the AIDS-cancer story has actually come full circle. It was the virus-cancer program conducted back in the 1970s and early 1980s that paved the way to better understanding of HIV/AIDS. "The development of our sophistication in virology and immunology, and the relationship between genetics, virology, and cancer, all came out of this infusion of money in the virus-cancer program; it did empower us ... to recognize that [AIDS] was a virus--and how it worked," says geneticist Stephen J. O'Brien of the National Cancer Institute (NCI). Anthony Fauci, director of the National Institute of Allergies and Infectious Diseases (NIAID), adds: "Now that AIDS has really opened up whole new fields of research, there is cross-fertilizing back to cancer. But what we know about AIDS really emanated from a lot of creative people many years ago investigating the relationship between viral genes, cellular genes, and cancer transformation." HIV-infected people have increased cancer incidence, with an estimated one-third of AIDS patients acquiring a malignancy. A few of these cancers have come to be known as AIDS cancers. "A variety of cancers are substantially increased with HIV infection, some dramatically, like Kaposi's sarcoma (KS) and lymphoma; others, including anal and genital cancers, and some say liver and even lung cancer, are statistically significant," says Robert Gallo, director of the Institute of Human Virology at the University of Maryland, and head of the tumor biology program at Baltimore Cancer Center. "As a result, we have more intense studies of these cancers, bringing many people into cancer research who wouldn't have been [there] at all." Because these cancers interact with the virus that targets the immune system, immunology of HIV has been another point of research focus. "HIV/AIDS has created ... an extraordinary opportunity to delve into the intricacies of the immune system, and the intensive research in this area is bringing about a better understanding of immunological surveillance and the ability of the immune system to protect against the emergence of certain cancers," Fauci comments. "And that will ultimately have ... benefits in understanding the relationship between neoplasms and the immune system, and the ... three-part relationship between the immune system, certain viruses, and cancers." For example, Fauci adds, certain cancers are associated with certain viral infections and with a certain degree of immunological control, or lack thereof, of the neoplastic process. "You get the herpes virus 8 (HHV-8) with KS, and papilloma virus with carcinoma of the cervix; these particular tumors have increased incidence and frequency in people who are immunosuppressed with HIV infection. It's complicated ... but it's an interesting window into understanding one or more aspects of neoplasms in cancer and how they relate to the immune system." Adds O'Brien of NCI: "As we learn more and more, we are finding there's an interaction between the environment, viruses, and genes that we might not have anticipated. AIDS research has taught us a lot about that. Before microbiology really got into cancer research in a big way, there were arguments about nature and nurture for a lot of things, from intelligence to diseases." Cancer, he points out, is no longer viewed as just involving a mutation in a gene that marks someone for the disease. Rather, cancer research has identified hundreds of genes, which if mutated increase the likelihood of a person getting cancer. "So it's a series of steps," O'Brien points out. "A lot of that has come from cancer research, but the understanding of AIDS, which has had an almost comparable amount of resources, has really given us a much richer understanding of the immune response." In the process, researchers are learning more about the mechanisms of the HIV/AIDS cancers. "We will probably learn more from HIV about indirect mechanisms that influence cancer than we have ... ever learned from combined research in all medical research history," asserts Gallo, who spent 20 years on "pure cancer research" at the NCI before beginning work on HIV/AIDS. While HIV does not directly cause cancer, it greatly influences cancer incidence. "So if you understand what HIV does, you will understand one mechanism of undoubtedly many mechanisms that can influence ... cancer," he observes. In fact, Gallo suggests, the immunodeficiency that is the hallmark of HIV may not be the only causal factor leading to these cancers. "HIV infection also leads to a surge in production of certain kinds of cytokines and growth factors ..., and perhaps that, rather than the immune deficiency per se, is causing KS and maybe some of these other HIV/AIDS cancers."1 HAF--human chorionic gonadotropin-associated factor--could be the first direct crossover from AIDS research to cancer therapy. Just purified several weeks ago, this small molecule found in the urine of women in the early stages of pregnancy was discovered accidentally at the Institute for Human Virology last year.2 In recent preliminary studies, it continues to show great promise for the treatment of various forms of cancer, including KS and prostate, as well as AIDS. "It kills tumor cells, blocks HIV replication, and promotes normal bone marrow growth," Gallo says. Though the discovery of HAF--soon to be renamed--was part of mice-model studies on KS, Gallo adds, "If it weren't for AIDS, we probably never would have studied KS and never would have discovered this." On the political front, the AIDS community produced the first patient activist network with a major impact, not only on patient awareness, but also on the scientists involved, the media, the public at large, celebrities, politicians, and even the U.S. Food and Drug Administration. In fact, Fauci, Gallo, and O'Brien all agree that the role of AIDS constituency advocacy in research agendas--specifically clinical trials--cannot be underestimated. "As a community, the HIV/AIDS patients had better, more informed attitudes about the value of research, [and] more selfless dedication than any others. I think that is transferring to patients of other diseases, especially cancer," O'Brien remarks. The approach of AIDS activists has also been influential. Just last fall, for example, the first "Cancer Day" was held in Washington, D.C. "This is the first time this has happened and they clearly took the lead from the AIDS community, which has been extremely well organized and extremely cooperative," O'Brien adds. "A lot of disease advocacies--including breast cancer and prostate cancer--have fashioned some of their own approaches and tactics according to what has been learned [from] the HIV/AIDS advocacy groups," adds Fauci. AIDS activism, meanwhile, all but transformed the media's attitude and approach to covering not only HIV/AIDS research, but also medical and scientific advances in general. "The media has turned around big time in the last 15 years, and that's because of AIDS," says O'Brien. Before AIDS research, medical research science almost never made it into the newspaper. These days it's almost every day. Moreover, he continues, with AIDS, "for the first time, journalists started to write in depth about incremental advances." The media's newfound interest in medical research science has been "an enormous help" in educating the public about all kinds of diseases and disorders, not the least of which are the various forms of cancer, O'Brien postulates. And as the media has become more sophisticated in interpreting what epidemiologists are reporting, and better at producing palatable and understandable articles for the public, the public has become better informed overall about risk factors associated with many diseases. For example, "to most people 25 years ago it wasn't clear that even tobacco was a risk factor for cancer," observes O'Brien. "It has empowered not only the public, but the people who represent the public, the legislators, to take a more proactive role and not be intimidated by what previously were mysterious workings in scientific laboratories." One of the most remarkable accomplishments of the HIV/AIDS advocacy community was to convince the FDA to speed up its approval process for drugs that look promising. O'Brien calls this "a social phenomenon" and hopes the same will happen with some of the promising cancer drugs. On a more subtle, less scientific level, the dedication of AIDS patients and activists has inspired scientists philosophically. In some cases, that inspiration stirred scientists to risk taking a path that might not otherwise have been taken; in other cases, it provoked them to consider the practicality of their research. "When I first started in my research studies in my small group trying to discover human genes that had something to do with cancer, the typical question I'd get from my colleagues was, 'What's the evidence that genes have anything to do with this?'" recalls O'Brien. "And I'd say, 'Well, there isn't any.' Today, they're all geneticists, they're all involved in it, and they're all working toward the same goal." Gallo, who acknowledges being "influenced very much" by Mark Delaney of Project Inform and by AIDS activist Larry Kramer, among others, experienced it this way: "They've made us consider that wherever we are in our research we should think about the practical possibilities. There is a correlating factor to that with the developments of modern biology and technology that have moved us into a region where we can go forward in practical matters much easier than [we could] 20 years ago. But the influence of these activists should be underscored, because they've also brought more understanding ... between population, patients, doctors, and scientists--getting rid of prejudices, for one thing." The resolute, sometimes-obstinate dedication of AIDS patients has not only given researchers plenty of data ammunition, it has also pierced the armor of "hard" scientists. "My [current] study of the genetic factors ..., information that is incredibly valuable for pharmaceutical companies trying to emulate these effects, wouldn't have happened without the absolute selfless dedication of these individuals," says O'Brien. "You've got to be moved by that no matter how cold-blooded a scientist you might be. We're beginning to see this same community now when people are hit by cancer. It's just a little less organized. But it's getting a lot better. And that's wonderful. And that's because of the impact of the AIDS community." A.J.S. Rayl is a freelance writer based in Malibu, Calif. E-mail: ajsrayl@loop.com R. Gallo, "The Enigmas of Kaposi's Sarcoma," Science, 282:1837-9, Dec. 4, 1998. A.J.S. Rayl, "War and Peace of Viruses Deliberated at Nobel Conference," The Scientist, 12[23]:1,7,13, Nov. 23, 1998.

Cancer and AIDS: A Symbiotic Relationship

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