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Is it time for a new paradigm for systemic cancer treatment? Lessons from a century of cancer chemotherapy

Crawford, Sarah·2013·Frontiers in Pharmacology
DOI 10.3389/fphar.2013.00068PMC PMC3691519
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FIGURE 1 Age-adjusted mortality rates for all cancers combined, US SEER data (Howlader et al., 2011).
FIGURE 1 Age-adjusted mortality rates for all cancers combined, US SEER data (Howlader et al., 2011).CC BY · PubMed Central
FIGURE 2 Age-adjusted mortality rates for specific cancer types in males and females, all races combined, US SEER data (Howlader et al., 2011).
FIGURE 2 Age-adjusted mortality rates for specific cancer types in males and females, all races combined, US SEER data (Howlader et al., 2011).CC BY · PubMed Central
FIGURE 3 Age-adjusted mortality rates for specific cancer types in females, all races combined, US SEER data (Howlader et al., 2011).
FIGURE 3 Age-adjusted mortality rates for specific cancer types in females, all races combined, US SEER data (Howlader et al., 2011).CC BY · PubMed Central
FIGURE 4 Age-adjusted mortality rates for specific cancer types in males, all races combined, US SEER data (Howlader et al., 2011).
FIGURE 4 Age-adjusted mortality rates for specific cancer types in males, all races combined, US SEER data (Howlader et al., 2011).CC BY · PubMed Central
FIGURE 5 Development of a successful combined chemotherapy approach for childhood acute lymphoblastic leukemia (ALL) that ultimately became a therapeutic model for the treatment of systemic cancers of many types. In 2012 the cure rate for childhood ALL is 90%. (Photo: Archive St. Jude’s Hospital). “November 12, 1970 – Dr. Rhomes J. A. Aur, of St. Jude Children’s Research Hospital, with Steven Ray of Jackson, Miss. who has been receiving treatment for leukemia for 2 years. Announcement of a 17% cure rate in leukemia was made at the hospital today.”
FIGURE 5 Development of a successful combined chemotherapy approach for childhood acute lymphoblastic leukemia (ALL) that ultimately became a therapeutic model for the treatment of systemic cancers of many types. In 2012 the cure rate for childhood ALL is 90%. (Photo: Archive St. Jude’s Hospital). “November 12, 1970 – Dr. Rhomes J. A. Aur, of St. Jude Children’s Research Hospital, with Steven Ray of Jackson, Miss. who has been receiving treatment for leukemia for 2 years. Announcement of a 17% cure rate in leukemia was made at the hospital today.”CC BY · PubMed Central
FIGURE 6 dUS SEER data on mortality rates of several leukemias and Hodgkin’s lymphoma that have seen a precipitous decline since 1975 resulting from dose-dense combined chemotherapy MTD therapies (Howlader et al., 2011).
FIGURE 6 dUS SEER data on mortality rates of several leukemias and Hodgkin’s lymphoma that have seen a precipitous decline since 1975 resulting from dose-dense combined chemotherapy MTD therapies (Howlader et al., 2011).CC BY · PubMed Central
FIGURE 7 Growth fraction model suggests that tumors consist of pools of both proliferating and non-proliferating cells, with only the former category possessing the intrinsic biological capacity to respond to drugs that specifically target dividing cells. Differential localization of cells within a solid tumor give rise to marked gradients in the rate of cell proliferation as a result of decreasing diffusion rates for oxygen, nutrients, and growth factors-associated abnormal vascularization of the solid tumor interior. Intrinsic chemotherapy resistance results when non-dividing cancer cells do not respond to S- and M-phase chemotherapy drugs that block cell proliferation by virtue of the fact that they are not in either the S- or M-phase of the cell cycle at the time of treatment (Komarova and Wodarz, 2005).
FIGURE 7 Growth fraction model suggests that tumors consist of pools of both proliferating and non-proliferating cells, with only the former category possessing the intrinsic biological capacity to respond to drugs that specifically target dividing cells. Differential localization of cells within a solid tumor give rise to marked gradients in the rate of cell proliferation as a result of decreasing diffusion rates for oxygen, nutrients, and growth factors-associated abnormal vascularization of the solid tumor interior. Intrinsic chemotherapy resistance results when non-dividing cancer cells do not respond to S- and M-phase chemotherapy drugs that block cell proliferation by virtue of the fact that they are not in either the S- or M-phase of the cell cycle at the time of treatment (Komarova and Wodarz, 2005).CC BY · PubMed Central
FIGURE 8 Physiological connections that may link cancer prevention and treatment. Excessive ROS (reactive oxygen species) due to aging or environmental exposure damage mitochondria and promote glycolytic switch characteristic of tumor cells. Inflammation and ROS activate NF-kB and other transcription factors that drive tumor progression. Anti-inflammatory agents and anti-oxidants prevent cancer by blocking systemic and microenvironmental changes that promote incipient tumor development and systemic disease progression. In the therapeutic setting, their long-term use restores systemic environment that blocks disease progression and/or recurrence.
FIGURE 8 Physiological connections that may link cancer prevention and treatment. Excessive ROS (reactive oxygen species) due to aging or environmental exposure damage mitochondria and promote glycolytic switch characteristic of tumor cells. Inflammation and ROS activate NF-kB and other transcription factors that drive tumor progression. Anti-inflammatory agents and anti-oxidants prevent cancer by blocking systemic and microenvironmental changes that promote incipient tumor development and systemic disease progression. In the therapeutic setting, their long-term use restores systemic environment that blocks disease progression and/or recurrence.CC BY · PubMed Central

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Metadata

Authors
Crawford, S.
Venue
Frontiers in Pharmacology
Publisher
Frontiers Media SA
Published
2013
Volume
4
ISSN
1663-9812
DOI
10.3389/fphar.2013.00068
PMC
PMC3691519
Cited by
108
References
5

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