E of social resources. We noted above a kind of social urgency, perhaps rooted in social Pyrvinium pamoate biological activity compassion that is attached to last chance therapies. Perhaps it is not really unreasonable for a society as wealthy as our own to pay 100,000 for patients who need access to these targeted therapies. However, our discussion of drug resistance in the face of the heterogeneity and genomic instability of many cancers, and the emerging commitment among researchers to follow the AIDS paradigm in attacking cancer, means that we ought to embrace the combinatorial strategy [33]. This will raise something of a conundrum. How will we know what is really the last chance therapy that deserves a very generous dose of social compassion? If we have in mind the sequential combinatorial version of targeted therapy, then we would be administering one of these very expensive targeted therapies until it was clear that the cancer was progressing, at which time we would switch to another of these drugs until the cancer progressed again, and perhaps there could be three or more such efforts before a patient succumbed. But then we are talking about expenditures of several hundred thousand dollars, each of which might be yielding only a marginal benefit for that patient. The same will be true, perhaps at even greater expense, if three targeted therapies are administered simultaneously, as with HIV triple therapy, in an effort to defeat multiple drivers of a cancer (hoping for longer periods of progression-free survival). Still, as with HIV therapy, the first combination will most likely be defeated by the cancer and require a different combination of these targeted drugs, now aimed at the emergent drivers of the cancer. As that combination is defeated yet another combination can be tried. Two possible concluding scenarios might be imagined at this point. In the first scenario the patient succumbs after cancer variants emerge for which there are no more targeted therapies. In the second scenario the cancer is kept at bay as a chronic disease with constant infusions of combinations of these targeted drugs for some number of years. In this latter scenario we might have to refrain from HIV-1 integrase inhibitor 2 biological activity describing the overall outcome as a marginal benefit, but the cost of achieving that outcome might be more than a million dollars per person. When considered in aggregate terms the costs become economically staggering. We might try to imagine the situation this way. There are almost 600,000 patients in the US who die of cancer each year. If that last year of life cost 100,000 for one or more of these targetable drugs, that would represent an expenditure for that cohort alone (no other cancer care for any other cancer patients) of 60 billion. But if we were successful in giving all those individuals an extra year of life for another 100,000 expenditure, that would raise the annual cost of providing cancer care to these terminally ill patients to 120 billion. If we achieved modest five-year success with this combinatorial strategy (modest relative to the fifteen year gains of many HIV patients on triple therapy), and if each of those extra years required only 100,000 worth of these drugs, then in year five we would be sustaining three million cancer patients at a cost of 300 billion per year only for addressing their cancer needs. If these patients had other health care needs, some of which might be related to side effects of prolonged use of these target therapies, then that would add to t.E of social resources. We noted above a kind of social urgency, perhaps rooted in social compassion that is attached to last chance therapies. Perhaps it is not really unreasonable for a society as wealthy as our own to pay 100,000 for patients who need access to these targeted therapies. However, our discussion of drug resistance in the face of the heterogeneity and genomic instability of many cancers, and the emerging commitment among researchers to follow the AIDS paradigm in attacking cancer, means that we ought to embrace the combinatorial strategy [33]. This will raise something of a conundrum. How will we know what is really the last chance therapy that deserves a very generous dose of social compassion? If we have in mind the sequential combinatorial version of targeted therapy, then we would be administering one of these very expensive targeted therapies until it was clear that the cancer was progressing, at which time we would switch to another of these drugs until the cancer progressed again, and perhaps there could be three or more such efforts before a patient succumbed. But then we are talking about expenditures of several hundred thousand dollars, each of which might be yielding only a marginal benefit for that patient. The same will be true, perhaps at even greater expense, if three targeted therapies are administered simultaneously, as with HIV triple therapy, in an effort to defeat multiple drivers of a cancer (hoping for longer periods of progression-free survival). Still, as with HIV therapy, the first combination will most likely be defeated by the cancer and require a different combination of these targeted drugs, now aimed at the emergent drivers of the cancer. As that combination is defeated yet another combination can be tried. Two possible concluding scenarios might be imagined at this point. In the first scenario the patient succumbs after cancer variants emerge for which there are no more targeted therapies. In the second scenario the cancer is kept at bay as a chronic disease with constant infusions of combinations of these targeted drugs for some number of years. In this latter scenario we might have to refrain from describing the overall outcome as a marginal benefit, but the cost of achieving that outcome might be more than a million dollars per person. When considered in aggregate terms the costs become economically staggering. We might try to imagine the situation this way. There are almost 600,000 patients in the US who die of cancer each year. If that last year of life cost 100,000 for one or more of these targetable drugs, that would represent an expenditure for that cohort alone (no other cancer care for any other cancer patients) of 60 billion. But if we were successful in giving all those individuals an extra year of life for another 100,000 expenditure, that would raise the annual cost of providing cancer care to these terminally ill patients to 120 billion. If we achieved modest five-year success with this combinatorial strategy (modest relative to the fifteen year gains of many HIV patients on triple therapy), and if each of those extra years required only 100,000 worth of these drugs, then in year five we would be sustaining three million cancer patients at a cost of 300 billion per year only for addressing their cancer needs. If these patients had other health care needs, some of which might be related to side effects of prolonged use of these target therapies, then that would add to t.