Overview of Research and Development for Anticancer Drugs

Download Download as PDF (Size:308KB)  HTML   XML  PP. 762-772  
DOI: 10.4236/jct.2016.710077    530 Downloads   749 Views  
Author(s)    Leave a comment


Anticancer drugs research and development have been the largest market area in the pharmaceutical industry in terms of the number of project, clinical trials and spending. In the last 10 - 30 years, targeting therapy for cancers has been developed and achieved enormous clinical effectiveness by transforming some previously deadly malignancies into chronically manageable conditions, but cure problem still remains. This mini review outlined the current status of anticancer drugs development and hinted the opinions of how to further increase the accuracy and efficacy of discovery for cancer treatment.

Cite this paper

Xu, J. and Mao, W. (2016) Overview of Research and Development for Anticancer Drugs. Journal of Cancer Therapy, 7, 762-772. doi: 10.4236/jct.2016.710077.


[1] Mehta, K., Gandhi, V., Pathak, S., Aggarwal, B.B. and Grover, R.K. (2014) Multi-Targeted Approach to Cancer Treatment: An International Translational Cancer Research Symposium. Anticancer Research, 34, 6791-6795.
[2] Moffat, J.G., Rudolph, J. and Bailey, D. (2014) Phenotypic Screening in Cancer Drug Discovery—Past, Present and Future. Nature Reviews Drug Discovery, 13, 588-602.
[3] Adams, D.J. (2012) The Valley of Death in Anticancer Drug Development: A Reassessment. Trends in Pharmacological Sciences, 33, 173-180.
[4] Bailón-Moscoso, N., Romero-Benavides, J.C. and Ostrosky-Wegman, P. (2014) Development of Anticancer Drugs Based on the Hallmarks of Tumor Cells. Tumor Biology, 35, 3981-3995.
[5] Widmer, N., Bardin, C., Chatelut, E., Paci, A., Beijnen, J., Levêque, D., et al. (2014) Review of Therapeutic Drug Monitoring of Anticancer Drugs Part Two—Targeted Therapies. European Journal of Cancer, 50, 2020-2036.
[6] Lim, S.H. and Levy, R. (2014) Translational Medicine in Action: Anti-CD20 Therapy in Lymphoma. The Journal of Immunology, 193, 1519-1524.
[7] Brown, C. (2016) Targeted Therapy: An Elusive Cancer Target. Nature, 537, S106-S108.
[8] Zhou, L., Xu, N., Sun, Y. and Liu, X.M. (2014) Targeted Biopharmaceuticals for Cancer Treatment. Cancer Letters, 352, 145-151.
[9] Herviou, P., Thivat, E., Richard, D., Roche, L., Dohou, J., Pouget, M., Eschalier, A., Durando, X. and Authier, N. (2016) Therapeutic Drug Monitoring and Tyrosine Kinase Inhibitors. Oncology Letters, 12, 1223-1232.
[10] Obenauf, A.C., Zou, Y., Ji, A.L., Vanharanta, S.N, Shu, W., Shi, H., et al. (2015) Therapy-Induced Tumour Secretomes Promote Resistance and Tumour Progressio. Nature, 520, 368-372.
[11] Juric, D., Castel, P., Griffith, M., Griffith, O.L., Won, H.H. and Ellis, H. (2015) Convergent Loss of PTEN Leads to Clinical Resistance to a PI(3)Kα Inhibitor. Nature, 518, 240-244.
[12] Lieu, C.H., Tan, A.C., Leong, S., Diamond, J.R. and Eckhardt, S.G. (2013) From Bench to Bedside: Lessons Learned in Translating Preclinical Studies in Cancer Drug Development. Journal of the National Cancer Institute, 105, 1441-1456.
[13] Ryall, K.A. and Tan, A.C. (2015) Systems Biology Approaches for Advancing the Discovery Of Effective Drug Combinations. Journal of Cheminformatics, 7, 7.
[14] Martz, C.A., Ottina, K.A., Singleton, K.R., Jasper, J.S., Wardell, S.E., Peraza-Penton, A., et al. (2014) Systematic Identification of Signaling Pathways with Potential to Confer Anticancer Drug Resistance. Science Signaling, 7, ra121.
[15] Crystal, A.S., Shaw, A.T., Sequist, L.V., Friboulet, L., Niederst, M.J., Lockerman, E.L., et al. (2014) Patient-Derived Models of Acquired Resistance Can Identify Effective Drug Combinations for Cancer. Science, 346, 1480-1486.
[16] Frangione, M.L., Lockhart, J.H., Morton, D.T., Pava, L.M. and Blanck, G. (2015) Anticipating Designer Drug-Resistant Cancer Cells. Drug Discovery Today, 20, 790-793.
[17] Tong, L., Chuang, C.C., Wu, S. and Zuo, L. (2015) Reactive Oxygen Species in Redox Cancer Therapy. Cancer Letters, 367, 18-25.
[18] Yang, W., Zou, L., Huang, C. and Lei, Y. (2014) Redox Regulation of Cancer Metastasis: Molecular Signaling and Therapeutic Opportunities. Drug Development Research, 75, 331-341.
[19] Gad, H., Koolmeister, T., Jemth, A.S., Eshtad, S., Jacques, S.A. and Strom, C.E. (2014) MTH1 Inhibition Eradicates Cancer by Preventing Sanitation of the dNTP Pool. Nature, 508, 215-222
[20] Kawagishi, H. and Finkel, T. (2014) Unraveling the Truth about Antioxidants: ROS and Disease: Finding the Right Balance. Nature Medicine, 20, 711-713.
[21] Sabharwal, S.S. and Schumacker, P.T. (2014) Mitochondrial ROS in Cancer: Initiators, Amplifiers or an Achilles’ Heel? Nature Reviews Cancer, 14, 709-721.
[22] Ristow, M. (2014) Unraveling the Truth about Antioxidants: Mitohormesis Explains ROS-Induced Health Benefits. Nature Medicine, 20, 709-711.
[23] Ibanez, I.L., Notcovich, C., Catalano, P.N., Bellino, M.G. and Durán, H. (2015) The Redox-Active Nanomaterial Toolbox for Cancer Therapy. Cancer Letters, 359, 9-19.
[24] Lu, M., Lawrence, D.A., Marsters, S., Acosta-Alvear, D., Kimmig, P., Mendez, A.S., et al. (2014) Opposing Unfolded-Protein-Response Signals Converge on Death Receptor 5 to Control Apoptosis. Science, 345, 98-101.
[25] Wang, M. and Kaufman, R.J. (2014) The Impact of the Endoplasmic Reticulum Protein-Folding Environment on Cancer Development. Nature Review Cancer, 14, 581-597.
[26] Hiramatsu, N., Chiang, W.C., Kurt, T.D., Sigurdson, C.J. and Lin, J.H. (2015) Multiple Mechanisms of Unfolded Protein Response-Induced Cell Death. American Journal of Pathology, 185, 1800-1808.
[27] Maas, N.L. and Diehl, J.A. (2015) Molecular Pathways: The PERKs and Pitfalls of Targeting the Unfolded Protein Response in Cancer. Clinical Cancer Research, 21, 675-679.
[28] Lee, A.S. (2014) Glucose-Regulated Proteins in Cancer: Molecular Mechanisms and Therapeutic Potential. Nature Review Cancer, 14, 263-276.
[29] Tan, J.S., Ong, K.K.C. and Rhodes, A. (2016) The Role of Heat Shock Proteins and Glucose Regulated Proteins in Cancer. Malaysian Journal of Pathology, 38, 75-82.
[30] Brüning, A. and Jückstock, J. (2015) Misfolded Proteins: From Little Villains to Little Helpers in the Fight against Cancer. Frontiers in Oncology, 5, 47.
[31] Solárová, Z., Mojzis, J. and Solár, P. (2015) Hsp90 Inhibitor as a Sensitizer of Cancer Cells to Different Therapies. International Journal of Oncology, 46, 907-926.
[32] Kukita, K., Tamura, Y., Tanaka, T., Kajiwara, T., Kutomi, G., Saito, K., et al. (2015) Cancer-Associated Oxidase ERO1-α Regulates the Expression of MHC Class I Molecule via Oxidative Folding. The Journal of Immunology, 194, 4988-4996.
[33] Tanaka, T., Kajiwara, T., Torigoe, T., Okamoto, Y., Sato, N. and Tamura, Y. (2015) Cancer-Associated Oxidoreductase ERO1-α Drives the Production of Tumor-Promoting Myeloid-Derived Suppressor Cells via Oxidative Protein Folding. The Journal of Immunology, 194, 2004-2010.
[34] Delaunay-Moisan, A. and Appenzeller-Herzog, C. (2015) The Antioxidant Machinery of the Endoplasmic Reticulum: Protection and Signaling. Free Radical Biology & Medicine, 83, 341-351.
[35] Clarke, H.J., Chambers, J.E., Liniker, E. and Marciniak, S.J. (2014) Endoplasmic Reticulum Stress in Malignancy. Cancer Cell, 25, 563-573.
[36] Hu, Z.Y., Xiao, L., Bode, A.M., Dong, Z. and Cao, Y. (2014) Glycolytic Genes in Cancer Cells Are More than Glucose Metabolic Regulators. Journal of Molecular Medicine, 92, 837-845.
[37] Michels, J., Obrist, F., Castedo, M., Vitale, I. and Kroemer, G. (2014) PARP and Other Prospective Targets for Poisoning Cancer Cell Metabolism. Biochemical Pharmacology, 92, 164-171.
[38] Augoff, K., Hryniewicz-Jankowska, A. and Tabola, R. (2015) Lactate Dehydrogenase 5: An Old Friend and a New Hope in the War on Cancer. Cancer Letters, 358, 1-7.
[39] Fiume, L., Manerba, M., Vettraino, M. and Di Stefano, G. (2014) Inhibition of Lactate Dehydrogenase Activity as an Approach to Cancer Therapy. Future Medicinal Chemistry, 6, 429-445.
[40] Yélamos, J., Galindo, M., Navarro, J., Albanell, J., Rovira, A., Rojo, F. and Oliver, J. (2015) Enhancing Tumor-Targeting Monoclonal Antibodies Therapy by PARP Inhibitors. Oncoimmunology, 5, e1065370.
[41] Rodríguez-Enríquez, S., Gallardo-Pérez, J.C., Hernández-Reséndiz, I., Marín-Hernández, A., Pacheco-Velázquez, S.C., López-Ramírez, S.Y., et al. (2014) Canonical and New Generation Anticancer Drugs Also Target Energy Metabolism. Archives of Toxicology, 88, 1327-1350.
[42] Bhat, T.A., Kumar, S., Chaudhary, A.K., Yadav, N. and Chandra, D. (2015) Restoration of Mitochondria Function as a Target for Cancer Therapy. Drug Discovery Today, 20, 635-643.
[43] Ji, D., Beharry, A.A., Ford, J.M. and Kool, E.T. (2016) A Chimeric ATP-Linked Nucleotide Enables Luminescence Signaling of Damage Surveillance by MTH1, a Cancer Target. Journal of the American Chemical Society, 138, 9005-9008.
[44] Huber, K.V., Salah, E., Radic, B., Gridling, M., Elkins, J.M., Stukalov, A., et al. (2014) Stereospecific Targeting of MTH1 by (S)-Crizotinib as an Anticancer Strategy. Nature, 508, 222-227.
[45] DuPage, M., Mazumdar, C., Schmidt, L.M., Cheung, A.F. and Jacks, T. (2012) Expression of tumour-Specific Antigens Underlies Cancer Immunoediting. Nature, 482, 405-409.
[46] Teng, M.W., Galon, J., Fridman, W.H. and Smyth, M.J. (2015) From Mice to Humans: Developments in Cancer Immunoediting. Journal of Clinical Investigation, 125, 3338-3346.
[47] Kareva, I. and Berezovskaya, F. (2015) Cancer Immunoediting: A Process Driven by Metabolic Competition as a Predator-Prey-Shared Resource Type Model. Journal of Theoretical Biology, 380, 463-472.
[48] Makkouk, A. and Weiner, G.J. (2015) Cancer Immunotherapy and Breaking Immune Tolerance: New Approaches to an Old Challenge. Cancer Research, 75, 5-10.
[49] Aranda, F., Vacchelli, E., Obrist, F., Eggermont, A., Galon, J., Sautès-Fridman, C., et al. (2014) Trial Watch: Toll-Like Receptor Agonists in Oncological Indications. Oncoimmunology, 3, e29179.
[50] Herbst, R.S., Soria, J.C., Kowanetz, M., Fine, G.D., Hamid, O., Gordon, M.S., et al. (2014) Predictive Correlates of Response to the Anti-PD-L1 Antibody MPDL3280A in Cancer Patients. Nature, 515, 563-567.
[51] Aranda, F., Vacchelli, E., Eggermont, A., Galon, J., Sautès-Fridman, C., Tartour, E., et al. (2013) Trial Watch: Peptide Vaccines in Cancer Therapy. Oncoimmunology, 2, e26621.
[52] Pauken, K.E. and Wherry, E.J. (2014) TIGIT and CD226: Tipping the Balance between Costimulatory and Coinhibitory Molecules to Augment the Cancer Immunotherapy Toolkit. Cancer Cell, 26, 785-787.
[53] Vacchelli, E., Aranda, F., Eggermont, A., Galon, J., Sautès-Fridman, C., Zitvogel, L., et al. (2014) Trial Watch: Tumor-Targeting Monoclonal Antibodies in Cancer Therapy. Oncoimmunology, 3, e27048.
[54] Zheng, Y., Dou, Y., Duan, L., Cong, C., Gao, A., Lai, Q., et al. (2015) Using Chemo-Drugs or Irradiation to Break Immune Tolerance and Facilitate Immunotherapy in Solid Cancer. Cellular Immunology, 294, 54-59.
[55] Gomez-Roca, C. and Delord, J.P. (2014) Emerging New Anticancer Therapies in 2013. Current Opinion in Oncology, 26, 357-362.
[56] Ivanova, T.S., Krupodorova, T.A., Barshteyn, V.Y., Artamonova, A.B. and Shlyakhovenko, V.A. (2014) Anticancer Substances of Mushroom Origin. Experimental Oncology, 36, 58-66.
[57] Powles, T., Eder, J.P., Fine, G.D., Braiteh, F.S., Loriot, Y., Cruz, C., et al. (2014) MPDL3280A (Anti-PD-L1) Treatment Leads to Clinical Activity in Metastatic Bladder Cancer. Nature, 515, 558-562.
[58] Tumeh, P.C., Harview, C.L., Yearley, J.H., Shintaku, I.P., Taylor, E.J., Robert, L., et al. (2014) PD-1 Blockade Induces Responses by Inhibiting Adaptive Immune Resistance. Nature, 515, 568-571.
[59] Naidoo, J., Page, D.B., Li, B.T., Connell, L.C., Schindler, K., Lacouture, M.E., Postow, M.A. and Wolchok, J.D. (2015) Toxicities of the Anti-PD-1 and Anti-PD-L1 Immune Checkpoint Antibodies. Annals of Oncology, 27, 1362.
[60] Hoffman, R.M. and Zhao, M. (2014) Methods for the Development of Tumor-Targeting Bacteria. Expert Opinion on Drug Discovery, 9, 741-750.
[61] Dhillon, S. (2015) Dinutuximab: First Global Approval. Drugs, 75, 923-927.
[62] Sharma, P. and Allison, J.P. (2015) The Future of Immune Checkpoint Therapy. Science, 348, 56-61.
[63] Shahabi, V., Postow, M.A., Tuck, D. and Wolchok, J.D. (2015) Immune-Priming of the Tumor Microenvironment by Radiotherapy: Rationale for Combination with Immunotherapy to Improve Anticancer Efficacy. American Journal of Clinical Oncology, 38, 90-97.
[64] André, N., Carré, M. and Pasquier, E. (2014) Metronomics: Towards Personalized Chemotherapy? Nature Reviews Clinical Oncology, 11, 413-431.
[65] Demaria, S., Pilones, K.A., Vanpouille-Box, C., Golden, E.B. and Formenti, S.C. (2014) The Optimal Partnership of Radiation and Immunotherapy: From Preclinical Studies to Clinical Translation. Radiation Research, 182, 170-181.
[66] Esposito, A., Criscitiello, C. and Curigliano, G. (2015) Immune Checkpoint Inhibitors with Radiotherapy and Locoregional Treatment: Synergism and Potential Clinical Implication. Current Opinion in Oncology, 27, 445-451.
[67] Regal, J.F., Dornfeld, K.J. and Fleming, S.D. (2016) Radiotherapy: Killing with Complement. Annals of Translational Medicine, 4, 94.

comments powered by Disqus

Copyright © 2017 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.