As a moral problem and requires a just resolution. Ultimately that

As a moral problem and requires a just resolution. Ultimately that resolution must be forged through a process of rational democratic deliberation. Keywords: personalized medicine; targeted therapies; oncology; cancer; health care justice; rational democratic deliberation; just caring problem; health care rationing1. Introduction It is reasonable to say that the age of personalized medicine and targeted therapies started with imatinib (Gleevec) for the treatment of GIST (Gastro Intestinal Stromal Tumor). The success of that drug was so astounding, and its perceived promise so enormous, that it made the cover of TIME magazineJ. Pers. Med. 2013,early in the new millennium [1]. However, this may have created an overly simplified and overly optimistic buy Lasalocid (sodium) picture of how other targeted therapies could be developed for other cancers. What has become clearer over the past few years is the extraordinary heterogeneity and resilience of tumors in the face of dozens of new targeted cancer therapies. This is the problem of cancer drug resistance. In the next part of this essay I will summarize the research that depicts the complexity of the problem of cancer drug resistance. This needs to be placed in the economic context of the problem of rapidly escalating health care costs both in the US and in Europe, the third part of this essay. In turn that needs to be placed within an ethical context: How should we fairly distribute access to needed health care for an enormous range of health care needs when we have only limited resources (money) to meet virtually unlimited health care needs (cancer and everything else)? This is what I have referred to in my own work as the Just Caring problem [2]. Multiple issues of health care justice will be identified and analyzed in the last part of this essay. A number of researchers have suggested that the ultimate strategy for addressing the heterogeneity of cancer will be a rational combinatorial approach [3?]. In other words, multiple drugs would be given at once to initially contain the cancer, and then they would be sequentially altered in response to the evolution of the tumor(s). This is a version of the strategy that works with HIV. But HIV is a virus, a much simpler Procyanidin B1 structure entity to manage (as actual clinical results have proven). It requires a considerable degree of optimism to believe that this same sort of success is achievable with regard to the enormously more complex biology of cancer. But even if this optimism proves to be well-founded, the economic and ethical costs that would be incurred ought to give us pause. 2. Heterogeneity, Targeted Therapies, and Drug Resistance The heterogeneity of individual cancers has been known for several decades [8,9]. Initially that heterogeneity was identified at the histological level. Today that heterogeneity is recognized at the molecular and genetic levels [10,11]. The heterogeneity is extraordinarily complex. It is not just a matter of genetic heterogeneity of tumors among individuals, each of whom has what would have been identified in the past as the same tumor. And it is more than genetic heterogeneity among tumors within the same individual. Rather, the genetic heterogeneity often exists within individual tumors [10,12]. Instead of tumor growth being linear, it appears more often as branched evolutionary growth [10]. Gerlinger et al. performed exome sequencing on a number of samples of primary renal carcinomas and associated metastatic sites, and found that 63 to 69 o.As a moral problem and requires a just resolution. Ultimately that resolution must be forged through a process of rational democratic deliberation. Keywords: personalized medicine; targeted therapies; oncology; cancer; health care justice; rational democratic deliberation; just caring problem; health care rationing1. Introduction It is reasonable to say that the age of personalized medicine and targeted therapies started with imatinib (Gleevec) for the treatment of GIST (Gastro Intestinal Stromal Tumor). The success of that drug was so astounding, and its perceived promise so enormous, that it made the cover of TIME magazineJ. Pers. Med. 2013,early in the new millennium [1]. However, this may have created an overly simplified and overly optimistic picture of how other targeted therapies could be developed for other cancers. What has become clearer over the past few years is the extraordinary heterogeneity and resilience of tumors in the face of dozens of new targeted cancer therapies. This is the problem of cancer drug resistance. In the next part of this essay I will summarize the research that depicts the complexity of the problem of cancer drug resistance. This needs to be placed in the economic context of the problem of rapidly escalating health care costs both in the US and in Europe, the third part of this essay. In turn that needs to be placed within an ethical context: How should we fairly distribute access to needed health care for an enormous range of health care needs when we have only limited resources (money) to meet virtually unlimited health care needs (cancer and everything else)? This is what I have referred to in my own work as the Just Caring problem [2]. Multiple issues of health care justice will be identified and analyzed in the last part of this essay. A number of researchers have suggested that the ultimate strategy for addressing the heterogeneity of cancer will be a rational combinatorial approach [3?]. In other words, multiple drugs would be given at once to initially contain the cancer, and then they would be sequentially altered in response to the evolution of the tumor(s). This is a version of the strategy that works with HIV. But HIV is a virus, a much simpler entity to manage (as actual clinical results have proven). It requires a considerable degree of optimism to believe that this same sort of success is achievable with regard to the enormously more complex biology of cancer. But even if this optimism proves to be well-founded, the economic and ethical costs that would be incurred ought to give us pause. 2. Heterogeneity, Targeted Therapies, and Drug Resistance The heterogeneity of individual cancers has been known for several decades [8,9]. Initially that heterogeneity was identified at the histological level. Today that heterogeneity is recognized at the molecular and genetic levels [10,11]. The heterogeneity is extraordinarily complex. It is not just a matter of genetic heterogeneity of tumors among individuals, each of whom has what would have been identified in the past as the same tumor. And it is more than genetic heterogeneity among tumors within the same individual. Rather, the genetic heterogeneity often exists within individual tumors [10,12]. Instead of tumor growth being linear, it appears more often as branched evolutionary growth [10]. Gerlinger et al. performed exome sequencing on a number of samples of primary renal carcinomas and associated metastatic sites, and found that 63 to 69 o.