Science, the UICC and global cancer control.

Abstract

The International Union Against Cancer (UICC) is a non-governmental organisation (NGO) that is devoted solely to the global control of cancer. Its membership is worldwide, as befits an organisation with global aspirations, but this membership is unevenly distributed. Most of its members are based in the wealthy developed countries of North America, western Europe, Australasia and Japan, and it is they who provide the bulk of UICC's financial support. In contrast, a number of developing countries in South and Central America, eastern Europe and Asia are not represented in the UICC, and only a minority of countries in Africa have UICC members. During the past few years, UICC has been reviewing its objectives in order to put its limited funds to best use in the global fight against cancer. A new strategy focuses resources where they are most needed; however, this raises concern that members in developed countries, where the need for UICC resources is less, might consider that UICC membership is of decreasing relevance to them. Many of these members are conducting research or delivering cancer services that are well resourced and at the leading edge of their scientific fields, and the activities of UICC might appear to be of little mutual benefit. In this short article, I argue that this is emphatically not the case and that first-rate science informs and enables cancer control and, in return, is nurtured by this process. In other words, the UICC needs organisations in the developed world, and these organisations can gain significant benefits from UICC membership. The International Agency for Research on Cancer (IARC) recently published its predictions for worldwide cancer incidence (International Agency for Research on Cancer,2003). They estimate that there will be almost 16 million new cancer cases in the year 2020, an increase of 5.6 million (55%) over the figure for 2000, and 70% of these cases will be in developing countries. This is not to belittle the problems that cancer will pose to the developed world, parts of which will show increases in cancer incidence of well over 50%, due in part to increased longevity and lifestyle risk factors, such as obesity. In the developed world, however, the five-year survival rate from all cancers is 50–60%, whereas it is only 30–40% in the developing world. For some cancers, there is a fivefold difference in five-year survival rates between the countries with the best and the worst health-care systems. Thus, although the developed world will face a challenge in trying to reduce both cancer incidence and mortality to the best levels achievable with current knowledge, the challenge is greatly magnified for the developing world. Indeed, since developing countries have only a small fraction of the world's convertible resources and many face the concomitant problems of population growth, environmental degradation and social instability, IARC's predictions are daunting. If we are to identify mutuality between the scientific community and the UICC, it is pertinent to ask how each approaches the issues raised by IARC's predictions. Overall, the approaches of the two are complementary rather than cooperative, with only minimal overlap. Nevertheless, when it comes to the problems of the developing world, which must shoulder the bulk of the cancer burden, even complementarity can be hard to find. The reasons for this disparity lie partly in differences in aims: between the broad, Promethean aims of much of the scientific enterprise and the focused, pragmatic ambitions of the UICC. Even more importantly, they reside with those who set the agenda for the scientific approach to cancer and who decide on the resources to be made available to scientific programmes on the one hand and to the UICC on the other. basic research into molecular and cellular biology, comparing the growth and behaviour of normal cells with their neoplastic counterparts and studying how carcinogenic events lead to cancer; strategic research, applying the knowledge acquired from basic research (often with model systems) to the biology of human cancers; translational research, converting knowledge acquired in the laboratory into new tools for cancer management; Clinical research, evaluating different means of diagnosis, curative and palliative treatment and psychosocial aspects of cancer; and population-based studies on cancer incidence and on professional and public awareness of the cancer problem. to elucidate the causes of cancer and hence to understand why some people develop cancer and others do not. This improves professional and public knowledge, leading to better cancer prevention and early detection. It thus benefits the whole population. to understand the mechanisms of the neoplastic process and how cancer arises and progresses. This leads to improved management of cancer patients at all stages of their disease. In the past 30 years of cancer research substantial progress has been made in basic and strategic research, as evidenced by our improved understanding of the nature of cancer, but less progress has been made in clinical and population research into cancer management, as exemplified by the failure significantly to improve overall cancer control, the objective of UICC. This has led to a burgeoning of translational research, to exploit experimental findings for the good of humanity as a whole and of cancer patient in particular. prevention and early detection, tobacco control, knowledge transfer and capacity building. The UICC is uniquely placed to meet these objectives, not only because of its global scope but also because of the breadth of its membership, which includes cancer societies, patient advocacy and support groups, public health authorities and research and treatment centres. The UICC thus has the same aims as the cancer research community, but it has a more focused approach to these aims and an active membership that extends far beyond the clinicians and researchers trained in scientific philosophy and method. The UICC is, quintessentially, a “boundary organisation” between science and policy, which links knowledge to action (International Council for Science,2002a). In many developed countries, this boundary role is fulfilled by national cancer organisations, but the UICC is the only body that exercises this function globally. It can therefore be the most influential voice for cancer control in much of the developing world. The unique nature of the UICC can be succinctly illustrated by the difference in the Union's approach to the cancer problem from that of the broad scientific community. Clinical and laboratory scientists would define success in translational research as offering the greatest promise for improving current best practice in cancer management. The UICC would further stress the equally important roles of advocacy and capacity building, tailored to the resources of individual countries and regions, with the eventual aim of eliminating disparities and offering all countries contemporary best practice in cancer control. As mentioned above, differences in the approaches of the UICC and the cancer research community are strongly influenced by those who set the agendas and allocate resources that the science community and UICC can command. Most scientific investigations are conducted in the developed world. Studies carried out in the public domain are funded by governments or charities; the balance of funding varies from country to country, but the premises behind the donation of funds are broadly similar. Considerable private resources are expended by pharmaceutical and biotechnology companies; however, although these bodies may work closely and to mutual benefit with publicly funded scientists, they do, of course, have other motives for their involvement. Each organisation that supports research has stakeholders, who ultimately provide the funds.These stakeholders, be they voters, donors or shareholders, are usually geographically localised. Naturally, they want the research to benefit them (albeit in different ways) and the society in which they live, and altruism is often attenuated when it extends beyond their locality, nation or region. As scientific research has to be justified to the stakeholders, not surprisingly, it tends to be concentrated on the problems posed by cancer in the developed world. The agenda of the UICC is set differently. Much of the funding comes from the same bodies that support national research, but the amount provided by any one body represents only a small fraction of that which it devotes to activities in its own country, thus reducing chauvinistic concerns. Moreover, as many researchers are aware of the worldwide need for cancer control, and increasing numbers of paymasters are sympathetic to addressing issues relevant to cancer in the developing world, funds are often (but by no means always) donated to the UICC with no restrictions on their use. UICC's stakeholders, too, are different, comprising many in the developing world, who ensure that the UICC takes a truly global perspective and does not look at cancer through the prism of developed countries' attitudes and interests. If the UICC is to tackle the predicted global cancer problem and exploit new knowledge successfully, its resources will have to be substantial and growing. In fact, the UICC's annual budget, US$ 5 million, represents a small percentage of the resources of major “first-world” voluntary organisations, such as the American Cancer Society and Cancer Research UK, which, in turn, are dwarfed by the expenditure of the United States National Cancer Institute. Clearly, the UICC is likely to make only a minute contribution to the accrual of new knowledge, and it accepts this. Indeed, the only research it supports that does not have an overt training component is translational research, through its Translational Cancer Research Fellowships, generously funded by several pharmaceutical companies. Any new knowledge otherwise gained is a by-product of the UICC's primary roles of capacity building, information dissemination and advocacy. These roles are, however, vitally dependent on the continual provision of new knowledge, which is best provided by collaboration with the institutions (mainly in the developed world) that generate the knowledge. Such interactions have added value for UICC in that they engage the voluntary participation of skilled workers in these institutions, thus maximising the use of UICC's limited funds. Indeed, the worldwide science community and the UICC must develop more points of contact, to benefit not only the UICC but, as I shall argue later, the scientific institutions themselves. It is abundantly clear that science, particularly population-based work, has already contributed immensely to global cancer control. All four of the UICC's strategic directions are firmly grounded in knowledge that was acquired and confirmed through the application of scientific methods. Scientific elucidation of the role of environmental carcinogens (particularly tobacco) and diet in cancer causation and of the role of diet in cancer protection optimises strategies for cancer prevention, which remain the most significant, cost-effective way to reduce the cancer burden worldwide. Basic, translational and clinical research have yet to deliver a comparable armoury in the fight against cancer, particularly in countries with few resources. They have, however, had some notable successes, some of the most promising of which are in prevention, screening and diagnosis. For instance, in a combination of population-based and molecular studies, several common infectious agents have been implicated as major human carcinogens, and modern techniques offer the prospect of vaccines against these agents. The question of immunisation against infectious carcinogens is complex (Neil & Wyke,1998), but programmes exist for immunoprevention of hepatitis B virus infections (which should also protect against primary hepatocellular carcinoma), and trials of both prophylactic and therapeutic vaccines for genital papillomaviruses are under way. Screening for certain cancers is now a common and successful procedure in developed countries. If the procedures can be made simpler and cheaper without sacrificing accuracy, they should become increasingly valuable for the developing world. This would, however, represent only a small gain unless affordable, effective treatments are also available. The present trends in the developed world towards ever more sophisticated therapies are not encouraging, and the potential increase in cost for new cancer therapies is a concern for even the richest nations. Such treatments would be unattainable for most of the developed world. The world's experience in tackling acquired immune deficiency syndrome (AIDS) is a sobering precedent: effective antiviral drugs have, until recently, been unaffordable in the countries where the AIDS problem is greatest and where the death toll increases unabated. The solutions are for pharmaceutical companies to offer discounted prices for developing nations or to licence companies in more advanced developing countries, such as Brazil and India, to produce affordable generic versions of the drugs. Similar international agreements will probably be required if new, effective cancer treatments are to have their full impact on global cancer control. The introduction of improved diagnostic procedures should, however, provide other ways of reducing the cost of treatment in both developed and developing countries. The DNA microarray technique permits genomic profiling of both patients and their tumours, which in the future could predict the response to therapy. This “pharmacogenomic” approach should enable treatment to be customised and thus prevent the wasteful application of ineffective or sub-optimal treatment. Again, such procedures will need to made simpler and cheaper if they are to be applied globally. The time necessary for creating truly novel treatments means that the cancer problem in the developing world will grow greatly before any novelty can make a significant contribution. For example, the drug “Glivec” which has impressive results against chronic myeloid leukaemia (CML), was put on the market almost 40 years after description of the Philadelphia marker chromosome in CML. Progress made during that time resulted in characterisation of the parentage of the Philadelphia chromosome, the genetic structure at the translocation breakpoints and the nature of the bcr–abl hybrid protein specified as a result of the translocation and against which “Glivec” acts. The accelerated pace of discovery nevertheless suggests that we may not need to wait as long before promising therapies based on genes such as Ras and P53 are made available. We must set against this the fact that “Glivec” targets a protein that is unique, being both specific to CML and required for its neoplastic nature. Other targets for novel treatments will be less accessible. Although it may be some time before the developing world gains new treatments from such research, this work does have benefits in capacity building. For instance, the research enterprise in the United States is a magnet for bright scientists and clinicians from China, the Indian subcontinent and elsewhere and, indeed, is increasingly reliant on this workforce. These expatriates, in turn, attract their fellow citizens, who return to their countries of origin where they greatly augment the skills base for both education and service delivery. This pattern (and comparable links between western and eastern Europe) is clearly reflected in UICC fellowships programmes such as the International Cancer Research Technology Transfer scheme, in which Fellows are obliged to return to their home countries. The UICC's strategic directions are closely interlinked. Capacity building in the developing world is key to prevention and tobacco control programmes in these regions. Capacity building means transferring knowledge and skills from those who have them to those who do not. The role of science in capacity building for sustainable development has been considered in detail in a series of recent publications by the International Council for Science (ICSU), a NGO that represents the world science community (International Council for Science,2002a, b, c). The ICSU stresses the importance of primary and secondary science education in the developing world, particularly for girls and women, who play vital roles in communities yet whose education is often neglected. The importance of collaboration, between developed and developing countries and among developing nations, is also stressed. Connections between the developed and developing world can be fostered by establishing international research centres in developing countries, by promoting international networks and programmes for capacity building and by mobilising expatriate scientists from developing countries who are based in the developed world. Although collaboration between developing nations would also be aided by networks and training programmes, it is important to strengthen links between science communities and politicians in developing countries (International Council for Science,2002b). Many of the recommendations made above are relevant to the problem of cancer control and the role of the UICC. The first step, training professionals based in the developing world, can be promoted by international fellowship programmes, such as those developed by the UICC. It will also be important to promote international networks of cancer professionals (also currently fostered by the UICC) and to establish cancer centres and research institutes in developing countries (a goal outside the financial capacity of the UICC but well within its scope as an advocate). Expatriates working in the developed world are already playing a valuable role in both training and advocacy, particularly since they understand and sympathise with the problems in their home nations. Once a cadre of cancer experts is established in a developing country, they will not only disseminate skills to fellow professionals and improve service delivery but will also add their voice to advocacy and raise awareness about cancer in the population. The UICC is well aware of the importance of ensuring that its messages reach the young and women. It is unlikely, however, that current “first world” approaches to the cancer problem will be directly applicable in most developing countries, where resources are limited. Local solutions may be needed for local problems, and, for those, a skilled workforce is essential, in order to adapt the practices of the developed world and to be alert to potential use of indigenous knowledge and resources. Traditional medicine still represents the primary health care for 80% of the world's population (WHO et al.,1993). As stated by the International Council for Science (2002d), “Disowning the role of traditional knowledge in medicine would disenfranchise a large majority of the world's population, ignore much of what constitutes modern medicine, and curtail discovery of new drugs and the treatment of diseases for which there is still no satisfactory cure”. In addition, the terrestrial and marine environments of the developing world contain much of the world's biodiversity. Thus, ‘bioprospecting’ for natural products with therapeutic potential could not only improve health care but also provide a resource for developing countries, if properly regulated. The promises and problems of exploiting traditional medicine and novel natural products have been discussed by Iwu and Wootton (2002) and Haefner (2003). In developing indigenous approaches to the cancer problem, it will be advantageous for cancer organisations in the developing world to build links with one another. In the first instance, these might evolve from links with regional enclaves of developed status, such as Singapore or the Gulf States. Regional caucuses of developing nations could help overcome the resource limitations that impede the application of science to cancer control. The strategic directions of the UICC apply to both developed and developing countries, albeit with qualitative and quantitative differences. For instance all parts of the world can learn from one another in tackling tobacco control and capacity building. Collaboration with institutions in the developing world, where there are different patterns of cancer incidence, can provide research problems and materials for ‘first world’ laboratory, clinical and population scientists, which are likely to add value to programmes addressing the problems of developed nations. To give one possible example, the rates of mortality from several cancers are higher in deprived than in affluent populations in developed countries, and these groups are often ethnic minorities. Appropriate international comparisons might help to disentangle the relative roles played by deprivation and ethnic group. Such collaboration could also provide useful access to indigenous resources, both local knowledge and biological materials, with experimental or therapeutic potential. Perhaps most importantly, developing countries represent a source of able, committed workers, eager to be trained in overseas institutions with funding from the UICC. Successful training programmes could lead to long-lasting, mutually valuable collaborations. In conclusion, the UICC must enhance the commitment of its members to strengthen the Union. A stronger UICC could then embark on building partnerships between its members in developed and developing countries, enhancing understanding of differing needs and priorities. Advances in electronic communication will increase the opportunities for worldwide interaction at low cost, which will enable the transfer of new knowledge and best practice, empowering the drive towards global cancer control. This aim will, however, be reached only if the institutions in the developed world that possess and expand knowledge and have the skill base play a full part in the UICC's activities. Most of this commentary is based on the self-evident common currency of cancer professionals, for which references are unnecessary or inappropriate. Where I have referred to less familiar areas or the data or arguments of others, I have referenced secondary rather than primary sources.