JCT  Vol.6 No.5 , May 2015
Pathogenesis of Cancer: Cancer Reparative Trap

Cancer is one of the leading causes of death in the world while the long-term prognosis is still unfavorable, despite the enormous efforts in the search for effective anti-cancer drugs. We think that the obstacle for creating of effective anti-cancer drugs could be existing idea that the basis of cancer is caused by the damage of the genetic apparatus of the cell. In this paper, we present the pathogenesis of cancer which is based on the formation of the special sustainable pathophysiological state of the organism what we call the state of “cancer reparative trap”. The essence of this pathophysiological state of the organism is in the reparative orientation of the immune system of cancer patients, when constant tissue repair is accompanied by systemic suppression of the anti-tumor immunity. Specifically, during the long-term exposure to carcinogens (exogenous and/or endogenous), the continuous tissue damage occurs which induces permanent stimulation of cell proliferation (imbalanced Th1 < Th2 lymphocytes, M1 < M2 macrophages, inflammation, angiogenesis, etc.) in order to repair the tissues damaged. At the same time, tissue repair is necessarily accompanied by the suppression of anti-tumor immunity (increase in T-regulatory cells, imbalanced Th1 < Th2 lymphocytes, M1 < M2 macrophages et al.), which creates the necessary conditions for the survival of the malignantly transformed cells, formed by the action of carcinogens. The determining role of the imbalance in the autonomous nervous system (simpathetic/hypersympathetic dominance) in the development, maintenance and generalization of the cancer process has been shown. The explanation of a number of phenomena has been presented: the cell resistance to chemotherapy, and the phenomenon of cancer cell dormancy. The promising approaches for the cancer management in clinical practice have been proposed.

Cite this paper
Bukhtoyarov, O. , Samarin, D. (2015) Pathogenesis of Cancer: Cancer Reparative Trap. Journal of Cancer Therapy, 6, 399-412. doi: 10.4236/jct.2015.65043.
[1]   Weinberg, R.A. (2006) The Biologу of Cancer. Garland Science, New York, 796 p.

[2]   Kushlinskii, N.E. and Nemtsova, M.V. (2014) Molecular Biological Characteristics of Cancer. Vestnik Rossiiskoi Akademii Meditsinskikh Nauk, 1-2, 5-15.

[3]   Bizzarri, M. and Cucina, A. (2014) Tumor and the Microenvironment: A Chance to Reframe the Paradigm of Carcinogenesis? BioMed Research International, 2014, Article ID: 934038.

[4]   Herbst, R.S., Bajorin, D.F., Bleiberg, H., Blum, D., Hao, D., Johnson, B.E., et al. (2006) Clinical Cancer Advances 2005: Major Research Advances in Cancer Treatment, Prevention, and Screening—A Report from the American Society of Clinical Oncology. Journal of Clinical Oncology, 24, 190-205.

[5]   Stewart, B.W. and Wild, C.P. (2014) World Cancer Report 2014. IARC Nonserial Publication (WHO), 630 p.

[6]   Pitot, H.C. and Dragan, Y.P. (1991) Facts and Theories Concerning the Mechanisms of Carcinogenesis. The FASEB Journal, 5, 2280-2286.

[7]   Halazonetis, T.D., Gorgoulis, V.G. and Bartek, J. (2008) An Oncogene-Induced DNA Damage Model for Cancer Development. Science, 319, 1352-1355.

[8]   Collisson, E.A., Cho, R.J. and Gray, J.W. (2012) What Are We Learning from the Cancer Genome? Nature Reviews Clinical Oncology, 9, 621-630.

[9]   Das, S.K., Menezes, M.E., Bhatia, S., Wang, X.Y., Emdad, L., Sarkar, D. and Fisher, P.B. (2015) Gene Therapies for Cancer: Strategies, Challenges and Successes. Journal of Cellular Physiology, 230, 259-271.

[10]   Lu, H., Ouyang, W. and Huang, C. (2006) Inflammation, a Key Event in Cancer Development. Molecular Cancer Research, 4, 221-233.

[11]   Prendergast, G.C. and Jaffee, E.M. (2007) Cancer Immunologists and Cancer Biologists: Why We Didn’t Talk Then but Need to Now. Cancer Research, 67, 3500-3504.

[12]   Poggi, A. and Zocchi, M.R. (2006) Mechanisms of Tumor Escape: Role of Tumor Microenvironment in Inducing Apoptosis of Cytolytic Effector Cells. Archivum Immunologiae et Therapiae Experimentalis (Warszawa), 54, 323-333.

[13]   Burkholder, B., Huang, R.Y., Burgess, R., Luo, S., Jones, V.S., Zhang, W., et al. (2014) Tumor-Induced Perturbations of Cytokines and Immune Cell Networks. Biochimica et Biophysica Acta, 1845, 182-201.

[14]   Vona-Davis, L. and Rose, D.P. (2007) Adipokines as Endocrine, Paracrine, and Autocrine Factors in Breast Cancer Risk and Progression. Endocrine Related Cancer, 14, 189-206.

[15]   Baccelli, I. and Trumpp, A. (2012) The Evolving Concept of Cancer and Metastasis Stem Cells. Journal of Cell Biology, 198, 281-293.

[16]   Ferretti, C., Bruni, L., Dangles-Marie, V., Pecking, A.P. and Bellet, D. (2007) Molecular Circuits Shared by Placental and Cancer Cells, and Their Implications in the Proliferative, Invasive and Migratory Capacities of Trophoblasts. Human Reproduction Update, 13,121-141.

[17]   Reuter, S., Gupta, S.C., Chaturvedi, M.M. and Aggarwal, B.B. (2010) Oxidative Stress, Inflammation, and Cancer: How Are They Linked? Free Radical Biology and Medicine, 49, 1603-1616.

[18]   Toyokuni, S., Okamoto, K., Yodoi, J. and Hiai, H. (1995) Persistent Oxidative Stress in Cancer. FEBS Letters, 358, 1-3.

[19]   Crawford, S. (2014) Anti-Inflammatory/Antioxidant Use in Long-Term Maintenance Cancer Therapy: A New Therapeutic Approach to Disease Progression and Recurrence. Therapeutic Advances in Medical Oncology, 6, 52-68.

[20]   Ng, S. and Galipeau, J. (2015) Concise Review: Engineering the Fusion of Cytokines for the Modulation of Immune Cellular Responses in Cancer and Autoimmune Disorders. Stem Cells Translational Medicine, 4, 66-73.

[21]   Ascierto, P.A., Addeo, R., Carteni, G., Daniele, B., De Laurentis, M., Ianniello, G., et al. (2014) The Role of Immunotherapy in Solid Tumors: Report from the Campania Society of Oncology Immunotherapy (SCITO) Meeting, Naples 2014. Journal of Translational Medicine, 12, 291.

[22]   Kenderian, S.S., Ruella, M., Gill, S. and Kalos, M. (2014) Chimeric Antigen Receptor T-Cell Therapy to Target Hematologic Malignancies. Cancer Research, 74, 6383-6389.

[23]   Westwood, J.A. and Kershaw, M.H. (2010) Genetic Redirection of T Cells for Cancer Therapy. Journal of Leukocyte Biology, 87, 791-803.

[24]   Pol, J., Bloy, N., Obrist, F., Eggermont, A., Galon, J., Hervé Fridman, W., et al. (2014) Trial Watch: DNA Vaccines for Cancer Therapy. Oncoimmunology, 3, Article ID: e28185.

[25]   Huang, Y., Goel, S., Duda, D.G., Fukumura, D. and Jain, R.K. (2013) Vascular Normalization as an Emerging Strategy to Enhance Cancer Immunotherapy. Cancer Research, 73, 2943-2948.

[26]   Jacobs, J.J., Snackey, C., Geldof, A.A., Characiejus, D., Van Moorselaar, R.J. and Den Otter, W. (2014) Inefficacy of Therapeutic Cancer Vaccines and Proposed Improvements. Casus of Prostate Cancer. Anticancer Research, 34, 2689-2700.

[27]   Mosser, D.M. and Edwards, J.P. (2008) Exploring the Full Spectrum of Macrophage Activation. Nature Reviews Immunology, 8, 958-969.

[28]   Martinez, F.O. and Gordon, S. (2014) The M1 and M2 Paradigm of Macrophage Activation: Time for Reassessment. F1000Prime Reports, 6, 13.

[29]   Barbul, A., Breslin, R.J., Woodyard, J.P., Wasserkrug, H.L. and Efron, G. (1989) The Effect of in Vivo T Helper and T Suppressor Lymphocyte Depletion on Wound Healing. Annals of Surgery, 209, 479-483.

[30]   Erenpreiss, J. (1993) Current Concepts of Malignant Growth. Part A: From a Normal Cell to Cancer. Zvaigzne Publishers, Riga, 191 p.

[31]   Boyce, D.E., Jones, W.D., Ruge, F., Harding, K.G. and Moore, K. (2000) The Role of Lymphocytes in Human Dermal Wound Healing. British Journal of Dermatology, 143, 59-65.

[32]   Ishida, Y., Kondo, T., Takayasu, T., Iwakura, Y. and Mukaida, N. (2004) The Essential Involvement of Cross-Talk Between IFN-γ and TGF-β in the Skin Wound Healing Process. Journal of Immunology, 172, 1848-1855.

[33]   Cao, Q., Wang, Y., Zheng, D., Sun, Y., Wang, Y., Lee, V.W., et al. (2010) IL-10/TGF-Beta-Modified Macrophages Induce Regulatory T Cells and Protect against Adriamycin Nephrosis. Journal of the American Society of Nephrology, 21, 933-942.

[34]   Duffield, J.S. (2003) The Inflammatory Macrophage: A Story of Jekyll and Hyde. Clinical Science, 104, 27-38.

[35]   Eming, S.A., Krieg, T. and Davidson, J.M. (2007) Inflammation in Wound Repair: Molecular and Cellular Mechanisms. Journal of Investigative Dermatology, 127, 514-525.

[36]   Traversa, B. and Sussman, G. (2001) The Role of Growth Factors, Cytokines and Proteases in Wound Management. Primary Intention: The Australian Journal of Wound Management, 9, 161-167.

[37]   Gratchev, A., Schledzewski, K., Guillot, P. and Goerdt, S. (2001) Alternatively Activated Antigen-Presenting Cells: Molecular Repertoire, Immune Regulation, and Healing. Skin Pharmacology and Applied Skin Physiology, 14, 272-279.

[38]   Smith, C., Kruger, M.J., Smith, R.M. and Myburgh, K.H. (2008) The Inflammatory Response to Skeletal Muscle Injury: Illuminating Complexities. Sports Medicine, 38, 947-969.

[39]   Lewis, C.J., Mardaryev, A.N., Sharov, A.A., Fessing, M.Y. and Botchkarev, V.A. (2014) The Epigenetic Regulation of Wound Healing. Advances in Wound Care (New Rochelle), 3, 468-475.

[40]   Agaiby, A.D. and Dyson, M. (1999) Immuno-Inflammatory Cell Dynamics during Cutaneous Wound Healing. Journal of Anatomy, 195, 531-542.

[41]   Gordon, S. and Martinez, F.O. (2010) Alternative Activation of Macrophages: Mechanism and Functions. Immunity, 32, 593-604.

[42]   Lech, M., Grobmayr, R., Weidenbusch, M. and Anders, H-J. (2012) Tissues Use Resident Dendritic Cells and Macrophages to Maintain Homeostasis and to Regain Homeostasis upon Tissue Injury: The Immunoregulatory Role of Changing Tissue Environments. Mediators of Inflammation, 2012, Article ID: 951390.

[43]   Ghiringhelli, F., Ménard, C., Martin, F. and Zitvogel, L. (2006) The Role of Regulatory T Cells in the Control of Natural Killer Cells: Relevance during Tumor Progression. Immunological Reviews, 214, 229-238.

[44]   Radosavljevic, G.D., Jovanovic, I.P., Kanjevac, T.V. and Arsenijevic, N.N. (2013) The Role of Regulatory T Cells in the Modulation of Anti-Tumor Immune Response. Srpski arhiv za celokupno lekarstvo (Serbian), 141, 262-267.

[45]   Bruno, A., Ferlazzo, G., Albini, A. and Noonan, D.M. (2014) A Think Tank of TINK/TANKs: Tumor-Infiltrating/Tumor-Associated Natural Killer Cells in Tumor Progression and Angiogenesis. Journal of the National Cancer Institute, 106, dju200.

[46]   Sloan, E.K., Priceman, S.J., Cox, B.F., Yu, S., Pimentel, M.A., Tangkanangnukul, V., et al. (2010) The Sympathetic Nervous System Induces a Metastatic Switch in Primary Breast Cancer. Cancer Research, 70, 7042-7052.

[47]   J?rgensen, A. (2013) Oxidatively Generated DNA/RNA Damage in Psychological Stress States. Danish Medical Journal, 60, Article ID: B4685.

[48]   Aschbacher, K., O’Donovan, A., Wolkowitz, O.M., Dhabhar, F.S., Su, Y. and Epel, E. (2013) Good Stress, Bad Stress and Oxidative Stress: Insights from Anticipatory Cortisol Reactivity. Psychoneuroendocrinology, 38, 1698-1708.

[49]   Flint, M.S. and Bovbjerg, D.H. (2012) DNA Damage as a Result of Psychological Stress: Implications for Breast Cancer. Breast Cancer Research, 14, 320.

[50]   Bukhtoyarov, O.V. and Samarin, D.M. (2009) Psychogenic Carcinogenesis: Carcinogenesis without Exogenic Carcinogens. Medical Hypotheses, 73, 531-536.

[51]   Bartsch, H. and Nair, J. (2006) Chronic Inflammation and Oxidative Stress in the Genesis and Perpetuation of Cancer: Role of Lipid Peroxidation, DNA Damage, and Repair. Langenbeck’s Archives Surgery, 391, 499-510.

[52]   Mantovani, A. (2010) Molecular Pathways Liking Inflammation and Cancer. Current Molecular Medicine, 10, 369-373.

[53]   Grivennikov, S.I., Greten, F.R. and Karin, M. (2010) Immunity, Inflammation, and Cancer. Cell, 140, 883-899.

[54]   Vaziri, H. and Benchimol, S. (1996) From Telomere Loss to p53 Induction and Activation of a DNA-Damage Pathway at Senescence: The Telomere Loss/DNA Damage Model of Cell Aging. Experimental Gerontology, 31, 295-301.

[55]   Shimizu, I., Yoshida, Y., Suda, M. and Minamino, T. (2014) DNA Damage Response and Metabolic Disease. Cell Metabolism, 20, 967-977.

[56]   Huang, J., Xie, Y., Sun, X., Zeh, H.J., Kang, R., Lotze, M.T. and Tang, D. (2014) DAMPs, Ageing, and Cancer: The “DAMP Hypothesis”. Ageing Research Reviews, 14, S1568-S1637.

[57]   Franceschi, C. and Campisi, J. (2014) Chronic Inflammation (Inflammaging) and Its Potential Contribution to Age-Associated Diseases. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 69, S4-S9.

[58]   Riggs, J.W., Barrilleaux, B.L., Varlakhanova, N., Bush, K.M., Chan, V. and Knoepfler, P.S. (2013) Induced Pluripotency and Oncogenic Transformation Are Related Processes. Stem Cells, 22, 37-50.

[59]   Upadhyay, M., Samal, J., Kandpal, M., Singh, O.V. and Vivekanandan, P. (2013) The Warburg Effect: Insights from the Past Decade. Pharmacology & Therapeutics, 137, 318-330.

[60]   Razungles, J., Cavaillès, V., Jalaguier, S. and Teyssier, C. (2013) The Warburg Effect: From Theory to Therapeutic Applications in Cancer. Médecine sciences (Paris), 29, 1026-1033.

[61]   Ito, K. and Suda, T. (2014) Metabolic Requirements for the Maintenance of Self-Renewing Stem Cells. Nature Reviews Molecular Cell Biology, 15, 243-256.

[62]   Lee, K.E. and Simon, M.C. (2012) From Stem Cells to Cancer Stem Cells: HIF Takes the Stage. Current Opinion in Cell Biology, 24, 232-235.

[63]   Natarajan, T.G., Ganesan, N. and Fitzgerald, K.T. (2010) Cancer Stem Cells and Markers: New Model of Tumorigenesis with Therapeutic Implications. Cancer Biomarkers, 9, 65-99.

[64]   Glenn, J.D. and Whartenby, K.A. (2014) Mesenchymal Stem Cells: Emerging Mechanisms of Immunomodulation and Therapy. World Journal of Stem Cells, 6, 526-539.

[65]   Ivanovic, Z. (2009) Hypoxia or in Situ Normoxia: The Stem Cell Paradigm. Journal of Cellular Physiology, 219, 271-275.

[66]   Riazi, A.M., Kwon, S.Y. and Stanford, W.L. (2009) Stem Cell Sources for Regenerative Medicine. Methods in Molecular Biology, 482, 55-90.

[67]   Lane, S.W., Williams, D.A. and Watt, F.M. (2014) Modulating the Stem Cell Niche for Tissue Regeneration. Nature Biotechnology, 32, 795-803.

[68]   Sell, S. (2004) Stem Cell Origin of Cancer and Differentiation Therapy. Critical Reviews in Oncology/Hematology, 51, 1-28.

[69]   Koukourakis, M.I., Giatromanolaki, A., Bougioukas, G. and Sivridis, E. (2007) Lung Cancer: A Comparative Study of Metabolism Related Protein Expression in Cancer Cells and Tumor Associated Stroma. Cancer Biology and Therapy, 6, 1476-1479.

[70]   Pavlides, S., Whitaker-Menezes, D., Castello-Cros, R., Flomenberg, N., Witkiewicz, A.K., Frank, P.G., et al. (2009) The Reverse Warburg Effect: Aerobic Glycolysis in Cancer Associated Fibroblasts and the Tumor Stroma. Cell Cycle, 8, 3984-4001.

[71]   Kasai, T., Chen, L., Mizutani, A., Kudoh, T., Murakami, H., Fu, L. and Seno, M. (2014) Cancer Stem Cells Converted from Pluripotent Stem Cells and the Cancerous Niche. Journal of Stem Cells and Regenerative Medicine, 10, 2-7.

[72]   Huggins, C. (1967) Endocrine-Induced Regression of Cancers. Science, 156, 1050-1054.

[73]   McCullough, K.D., Coleman, W.B., Smith, G.J. and Grisham, J.W. (1997) Age-Dependent Induction of Hepatic Tumor Regression by the Tissue Microenvironment after Transplantation of Neoplastically Transformed Rat Liver Epithelial Cells into the Liver. Cancer Research, 57, 1807-1813.

[74]   Maffini, M.V., Calabro, J.M., Soto, A.M. and Sonnenschein, C. (2005) Stromal Regulation of Neoplastic Development: Age-Dependent Normalization of Neoplastic Mammary Cells by Mammary Stroma. American Journal of Pathology, 167, 1405-1410.

[75]   Folkman, J. and Kalluri, R. (2004) Cancer without Disease. Nature, 427, 787.

[76]   Aguirre-Ghiso, J.A. (2007) Models, Mechanisms and Clinical Evidence for Cancer Dormancy. Nature Reviews Cancer, 7, 834-846.

[77]   Sosa, M.S., Bragado, P. and Aguirre-Ghiso, J.A. (2014) Mechanisms of Disseminated Cancer Cell Dormancy: An Awakening Field. Nature Reviews Cancer, 14, 611-622.

[78]   Manjili, M.H. (2014) The Inherent Premise of Immunotherapy for Cancer Dormancy. Cancer Research, 74, 1-5.

[79]   Chambers, A.F., Groom, A.C. and MacDonald, I.C. (2002) Dissemination and Growth of Cancer Cells in Metastatic Sites. Nature Reviews Cancer, 2, 563-572.

[80]   Mehlen, P. and Puisieux, A. (2006) Metastasis: A Question of Life or Death. Nature Reviews Cancer, 6, 449-458.

[81]   Luzzi, K.J., MacDonald, I.C., Schmidt, E.E., Kerkvliet, N., Morris, V.L., Chambers, A.F. and Groom, A.C. (1998) Multistep Nature of Metastatic Inefficiency: Dormancy of Solitary Cells after Successful Extravasation and Limited Survival of Early Micrometastases. American Journal of Pathology, 153, 865-873.

[82]   Kleffel, S. and Schatton, T. (2013) Tumor Dormancy and Cancer Stem Cells: Two Sides of the Same Coin? Advances in Experimental Medicine and Biology, 734, 145-179.

[83]   El Saghir, N.S., Elhajj, I.I., Geara, F.B. and Hourani, M.H. (2005) Trauma-Associated Growth of Suspected Dormant Micrometastasis. BMC Cancer, 5, 94.

[84]   Demicheli, R., Retsky, M.W., Hrushesky, W.J. and Baum, M. (2007) Tumor Dormancy and Surgery-Driven Interruption of Dormancy in Breast Cancer: Learning from Failures. Nature Clinical Practice Oncology, 4, 699-710.

[85]   Mocellin, S. and Nitti, D. (2008) Therapeutics Targeting Tumor Immune Escape: Towards the Development of New Generation Anticancer Vaccines. Medicinal Research Reviews, 28, 413-444.

[86]   Mittal, D., Gubin, M.M., Schreiber, R.D. and Smyth, M.J. (2014) New Insights into Cancer Immunoediting and Its Three Component Phases—Elimination, Equilibrium and Escape. Current Opinion in Immunology, 27, 16-25.

[87]   Corthay, A. (2014) Does the Immune System Naturally Protect Against Cancer? Frontiers in Immunology, 5, 197.

[88]   Gajewski, T.F., Woo, S.R., Zha, Y., Spaapen, R., Zheng, Y., Corrales, L. and Spranger, S. (2013) Cancer Immunotherapy Strategies Based on Overcoming Barriers within the Tumor Microenvironment. Current Opinion in Immunology, 25, 268-276.

[89]   Yi, D.H. and Appel, S. (2013) Current Status and Future Perspectives of Dendritic Cell-Based Cancer Immunotherapy. Scandinavian Journal of Immunology, 78, 167-171.

[90]   Mougiakakos, D., Choudhury, A., Lladser, A., Kiessling, R. and Johansson, C.C. (2010) Regulatory T Cells in Cancer. Advances in Cancer Research, 107, 57-117.

[91]   Oleinika, K., Nibbs, R.J., Graham, G.J. and Fraser, A.R. (2013) Suppression, Subversion and Escape: The Role of Regulatory T Cells in Cancer Progression. Clinical and Experimental Immunology, 171, 36-45.

[92]   López, M., Aguilera, R., Pérez, C., Mendoza-Naranjo, A., Pereda, C., Ramirez, M., et al. (2006) The Role of Regulatory T Lymphocytes in the Induced Immune Response Mediated by Biological Vaccines. Immunobiology, 211, 127-136.

[93]   Song, S., Zhang, K., You, H., Wang, J., Wang, Z., Yan, C. and Liu, F. (2010) Significant Anti-Tumour Activity of Adoptively Transferred T Cells Elicited by Intratumoral Dendritic Cell Vaccine Injection through Enhancing the Ratio of CD8+ T Cell/Regulatory T Cells in Tumour. Clinical and Experimantal Immunology, 162, 75-83.

[94]   Parmiani, G., Pilla, L., Maccalli, C. and Russo, V. (2011) Autologous versus Allogeneic Cell-Based Vaccines? Cancer Journal, 17, 331-336.

[95]   Fujiwara, S., Wada, H., Miyata, H., Kawada, J., Kawabata, R., Nishikawa, H., et al. (2012) Clinical Trial of the Intratumoral Administration of Labeled DC Combined with Systemic Chemotherapy for Esophageal Cancer. Journal of Immunotherapy, 35, 513-521.

[96]   Longley, D.B. and Johnston, P.G. (2005) Molecular Mechanisms of Drug Resistance. Journal of Pathology, 205, 275-292.

[97]   Rebucci, M. and Michiels, C. (2013) Molecular Aspects of Cancer Cell Resistance to Chemotherapy. Biochemical Pharmacology, 85, 1219-1226.

[98]   Salehan, M.R. and Morse, H.R. (2013) DNA Damage Repair and Tolerance: A Role in Chemotherapeutic Drug Resistance. British Journal of Biomedical Science, 70, 31-40.

[99]   Sebens, S. and Schafer, H. (2012) The Tumor Stroma as Mediator of Drug Resistance—A Potential Target to Improve Cancer Therapy? Current Pharmaceutical Biotechnology, 13, 2259-2272.

[100]   Gordon, R.R. and Nelson, P.S. (2012) Cellular Senescence and Cancer Chemotherapy Resistance. Drug Resistance Updates, 15, 123-131.

[101]   Wang, Z. and Chen, W. (2013) Emerging Roles of SIRT1 in Cancer Drug Resistance. Genes and Cancer, 4, 82-90.

[102]   Ravindran Menon, D., Das, S., Krepler, C., Vultur, A., Rinner, B., Schauer, S., et al. (2014) A Stress-Induced Early Innate Response Causes Multidrug Tolerance in Melanoma. Oncogene, Published Online.

[103]   Li, S., Kennedy, M., Payne, S., Kennedy, K., Seewaldt, V.L., Pizzo, S.V. and Bachelder, R.E. (2014) Model of Tumor Dormancy/Recurrence after Short-Term Chemotherapy. PLoS ONE, 9, e98021.

[104]   Naito, M., Aisu, N., Maki, K., Nakagawa, M., Yoshida, Y., Hoshino, S. and Yamashita, Y. (2014) A Case of Unresected Gastric Cancer That Maintained Long Tumor Dormancy by Use of Paclitaxel+S-1 Combination Therapy. Gan to Kagaku Ryoho, 41, 241-244.

[105]   Mitchell, T. and Turton, P. (2011) “Chemobrain”: Concentration and Memory Effects in People Receiving Chemotherapy—A Descriptive Phenomenological Study. European Journal of Cancer Care, 20, 539-548.

[106]   Areti, A., Yerra, V.G., Naidu, V. and Kumar, A. (2014) Oxidative Stress and Nerve Damage: Role in Chemotherapy Induced Peripheral Neuropathy. Redox Biology, 2, 289-295.

[107]   Anderson, B. and Sawyer, D.B. (2008) Predicting and Preventing the Cardiotoxicity of Cancer Therapy. Expert Review of Cardiovascular Therapy, 6, 1023-1033.

[108]   Abid, S.H., Malhotra, V. and Perry, M.C. (2001) Radiation-Induced and Chemotherapy-Induced Pulmonary Injury. Current Opinion in Oncology, 13, 242-248.

[109]   Andreyev, H.J. (2010) A Physiological Approach to Modernize the Management of Cancer Chemotherapy-Induced Gastrointestinal Toxicity. Current Opinion in Supportive and Palliative Care, 4, 19-25.

[110]   Al-Tweigeri, T., Nabholtz, J.M. and Mackey, J.R. (1996) Ocular Toxicity and Cancer Chemotherapy: A Review. Cancer, 78, 1359-1373.

[111]   Kalialis, L.V., Drzewiecki, K.T. and Klyver, H. (2009) Spontaneous Regression of Metastases from Melanoma: Review of the Literature. Melanoma Research, 19, 275-282.

[112]   Jessy, T. (2011) Immunity over Inability: The Spontaneous Regression of Cancer. Journal of Natural Science, Biology and Medicine, 2, 43-49.

[113]   Papac, R.J. (1998) Spontaneous Regression of Cancer: Possible Mechanisms. In Vivo, 12, 571-578.

[114]   Lagova, N.D. (1978) Mechanism of Mammary Cancer Regression in Lactating Rats. Biulleten Eksperimentalnoi Biologii I Meditsiny (Moskva), 85, 582-585.

[115]   Buijs, M., Geschwind, J.F., Syed, L.H., Ganapathy-Kanniappan, S., Kunjithapatham, R., Wijlemans, J.W., et al. (2012) Spontaneous Tumor Regression in a Syngeneic Rat Model of Liver Cancer: Implications for Survival Studies. Journal of Vascular and Interventional Radiology, 23, 1685-1691.

[116]   Chang, W.Y. (2000) Complete Spontaneous Regression of Cancer: Four Case Reports, Review of Literature, and Discussion of Possible Mechanisms Involved. Hawaii Medical Journal, 59, 379-387.

[117]   Bukhtoyarov, O.V. and Samarin, D.M. (2012) Psychogenic Carcinogenesis. In: Mohan, R., Ed., Advances in Cancer Management, InTech, Rijeka, 17-56.

[118]   Moser, R.P., Arndt, J., Han, P.K., Waters, E.A., Amsellem, M. and Hesse, B.W. (2014) Perceptions of Cancer as a Death Sentence: Prevalence and Consequences. Journal of Health Psychology, 19, 1518-1524.

[119]   Bukhtoyarov, O.V. and Samarin, D.M. (2013) Psychogenic Activation Phenomenon of Specific Anti-Tumor Immunity in Cancer Patients. International Journal of Medicine and Medical Sciences, 5, 198-205.

[120]   Ikemi, Y., Nakagawa, S., Nagakawa, T. and Sugita, M. (1975) Psychosomatic Consideration on Cancer Patients Who Have Made a Narrow Escape from Death. Dynamic Psychiatry, 8, 77-91.

[121]   Niakan, B. (1998) A Mechanism of the Spontaneous Remission and Regression of Cancer. Cancer Biotherapy and Radiopharmaceuticals, 13, 209-210.

[122]   MаcAdam, D. (2003) Spontaneous Regression: Cancer and the Immune System. Replica Books, New York, 164 p.

[123]   Zhong, H., Han, B., Tourkova, I.L., Lokshin, A., Rosenbloom, A., Shurin, M.R. and Shurin, G.V. (2007) Low-Dose Paclitaxel Prior to Intratumoral Dendritic Cell Vaccine Modulates Intratumoral Cytokine Network and Lung Cancer Growth. Clinical Cancer Research, 13, 5455-5462.

[124]   Bukhtoyarov, O.V. and Samarin, D.M. (2013) Psycho-Immunological Rehabilitation of Advanced Cancer Patients with Psychogenic Medical History. Journal of Medicine and Medical Sciences, 5, 489-502.