By Beverly A. Teicher
Major specialists summarize and synthesize the most recent discoveries about the alterations that ensue in tumor cells as they improve resistance to anticancer medicines, and recommend new methods to fighting and overcoming it. The authors evaluation physiological resistance established upon tumor structure, mobile resistance in response to drug delivery, epigenetic alterations that neutralize or skip drug cytotoxicity, and genetic alterations that regulate drug aim molecules via lowering or doing away with drug binding and efficacy. Highlights comprise new insights into resistance to antiangiogenic remedies, oncogenes and tumor suppressor genes in healing resistance, melanoma stem cells, and the advance of greater treatments. There also are new findings on tumor immune get away mechanisms, gene amplification in drug resistance, the molecular determinants of multidrug resistance, and resistance to taxanes and Herceptin.
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Additional info for Cancer Drug Resistance (Cancer Drug Discovery and Development)
The results suggest that successful therapies should selectively target HIF-1 and/or its downstream target genes, such as VEGF, in order to break this cycle of interdependency. ACKNOWLEDGMENTS This work was supported by grants from the NCI (CA40355) and the Duke SPORE for breast cancer. The authors appreciate the editorial review of this manuscript by Catherine Sullivan and the confocal image of tumor microvascular intussusception provided by Matthew Dreher for Fig. 3. REFERENCES 1. Kraus RM, Stallings HW III, Yeager RC, Gavin, TP.
Dewhirst MW, Ong ET, Braun RD, et al. Quantification of longitudinal tissue pO2 gradients in window chamber tumours: impact on tumour hypoxia. Br J Cancer 1999; 79:1717–1722. 57. Secomb TW, Hsu R, Braun RD, Ross JR, Gross JF, Dewhirst MW. Theoretical simulation of oxygen transport to tumors by three-dimensional networks of microvessels. Adv Exp Med Biol 1998; 454:629–634. 58. Dewhirst MW, Secomb TW, Ong ET, Hsu R, Gross JF. Determination of local oxygen consumption rates in tumors. Cancer Res 1994; 54:3333–3336.
The relationship between extracellular pH (pHe) and intracellular pH (pHi) in human, rat and mouse tumors in situ. Both pHe and pHi in the same tumors were determined with magnetic resonance imaging/magnetic resonance spectroscopy method. Data reported by ref. 6 were used to construct this figure. and rat tumors determined with MRS/magnetic resonance imaging method and reviewed by Gilles (6). It can be seen that the pHi values are higher than the pHe values in the same tumors in all tumors studied.
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