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Combination Approach: the Future of the War Against Cancer

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Abstract

Cancer remains one of the major health problems worldwide and is responsible for one in eight deaths. The worldwide research against cancer as well as genome wide association studies was successful in indentifying the loci associated with cancer but still a substantial amount of casualty remains unexplained. The reason being the cancer cell rapidly develops resistance against the chemotherapeutic or chemopreventive agent in use. Over the last decade, the thorough understanding of molecular and biochemical mechanisms of the carcinogenesis process lead to the rationale of combining anti-cancer agents (therapeutic as well as chemopreventive) to target multiple pathways. Scientists, the world over trying various combinations of chemotherapy, radiation therapy, chemopreventive agents, nanoparticles, etc., in order to specifically as well as efficiently target cancer cells. The present review article summarizes the recent advances in the combination approach against cancer in order to enhance efficacy of treatment with minimal side effects.

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References

  1. Davis, M. E., Chen, Z. G., & Shin, D. M. (2008). Nanoparticle therapeutics: An emerging treatment modality for cancer. Nature Reviews Drug Discovery, 7(9), 771–782.

    Article  CAS  PubMed  Google Scholar 

  2. Lehar, J., Krueger, A. S., & Avery, W. (2009). Synergistic drug combinations tend to improve therapeutically relevant selectivity. Nature Biotechnology, 27(7), 659–666.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Lippman, S. M., Benner, S. E., & Hong, W. K. (1994). Cancer chemoprevention. Journal of Clinical Oncology, 12, 851–873.

    CAS  PubMed  Google Scholar 

  4. Donaldson, M. S. (2004). Nutrition and cancer: A review of the evidence for an anti-cancer diet. Nutrition Journal, 2004(3), 19.

    Article  Google Scholar 

  5. DeVita, V. (1997). Principles of cancer management: Chemotherapy. In V. DeVita, S. Hellman, & S. Rosenberg (Eds.), Cancer: Principles & practice of oncology (pp. 333–347). Philadelphia: Lippincott-Raven.

    Google Scholar 

  6. Malhotra, A., Nair, P., & Dhawan, D. K. (2014). Study to evaluate molecular mechanics behind synergistic chemo-preventive effects of curcumin and resveratrol during lung carcinogenesis. PLoS One, 9(4), e93820.

    Article  PubMed Central  PubMed  Google Scholar 

  7. Malhotra, A., Nair, P., & Dhawan, D. K. (2011). Curcumin and resveratrol synergistically stimulate p21 and regulate cox 2 by maintaining adequate zinc levels during lung carcinogenesis. European Journal of Cancer Prevention, 20(5), 411–416.

    Article  CAS  PubMed  Google Scholar 

  8. Malhotra, A., Nair, P., & Dhawan, D. K. (2012). Curcumin and resveratrol in combination modulates benzo[a]pyrene induced genotoxicity during lung carcinogenesis. Human and Experimental Toxicology, 31(12), 1199–1206.

    Article  CAS  PubMed  Google Scholar 

  9. Malhotra, A., Nair, P., & Dhawan, D. K. (2012). Premature mitochondrial senescence and related ultrastructural changes during lung carcinogenesis modulation by curcumin and resveratrol. Ultra Structural Pathology, 36(3), 179–184.

    Article  Google Scholar 

  10. Brenner, D. E. (2000). Multiagent chemopreventive agent combinations. Journal of Cellular Biochemistry Supplement, 34, 121–124.

    Article  CAS  PubMed  Google Scholar 

  11. Adom, K. K., & Liu, R. H. (2002). Antioxidant activity of grains. Journal of Agricultural Food Chemistry, 50, 6182–6187.

    Article  CAS  PubMed  Google Scholar 

  12. Chu, Y. F., Sun, J., Wu, X., & Liu, R. H. (2002). Antioxidant and antiproliferative activities of vegetables. Journal of Agriculture Food Chemistry, 50, 6910–6916.

    Article  CAS  Google Scholar 

  13. Sun, J., Chu, Y. F., Wu, X., & Liu, R. H. (2002). Antioxidant and antiproliferative activities of fruits. Journal of Agricultural Food Chemistry, 50, 7449–7454.

    Article  CAS  PubMed  Google Scholar 

  14. Kowalczyk, M. C., Kowalczyk, P., Tolstykh, O., & Slaga, T. J. (2010). Synergistic effects of combined phytochemicals and skin cancer prevention in SENCAR mice. Cancer Prevention Research, 3(2), 170–178.

    Article  CAS  PubMed  Google Scholar 

  15. Cunningham, D., Allum, W. H., & Stenning, S. P. (2006). Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. New England Journal of Medicine, 355(1), 11–20.

    Article  CAS  PubMed  Google Scholar 

  16. Ychou, M., Boige, V., & Pignon, J. P. (2011). Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: An FNCLCC and FFCD multicenter phase III trial. Journal of Clinical Oncology, 29(13), 1715–1721.

    Article  CAS  PubMed  Google Scholar 

  17. Thuss-Patience, P. C., Hofheinz, R. D., & Arnold, D. (2010). Perioperative chemotherapy with docetaxel, cisplatin, and capecitabine (DCX) in gastroesophageal adenocarcinoma: A phase II study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Annals of Oncology, 23(11), 2827–2834.

    Article  Google Scholar 

  18. Ferri, L. E., Ades, S., & Alcindor, T. (2010). Perioperative docetaxel, cisplatin, and 5-FU (DCF) for locally advanced esophageal and gastric adenocarcinoma: A multicenter phase II trial. Annals of Oncology, 23(6), 1512–1517.

    Article  Google Scholar 

  19. Zhang, X., Shen, L., Li, J., Li, Y., Li, J., & Jin, M. (2008). A phase II trial of paclitaxel and cisplatin in patients with advanced squamous-cell carcinoma of the esophagus. American Journal of Clinical Oncology, 31(1), 29–33.

    Article  PubMed  Google Scholar 

  20. Lordick, F., Luber, B., & Lorenzen, S. (2010). Cetuximab plus oxaliplatin/leucovorin/5-FU in first-line metastatic gastric cancer: A phase II study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Brazilian Journal of Cancer, 102(3), 500–505.

    Article  CAS  Google Scholar 

  21. Jagetia, G. C. (2007). Radioprotection and radiosensitization by curcumin. Advance Experimental Medicine Biology, 595, 301–320.

    Article  Google Scholar 

  22. Yallapu, M. M., Maher, D. M., Sundram, V., Bell, M. C., Jaggi, M., & Chauhan, S. C. (2010). Curcumin induces chemo/radio-sensitization in ovarian cancer cells and curcumin nanoparticles inhibit ovarian cancer cell growth. Journal of Ovarian Research, 29, 3–11.

    Google Scholar 

  23. Lin, X., Zhang, F., Bradbury, C. M., Kaushal, A., Li, L., Spitz, D. R., et al. (2003). 2-Deoxy-d-glucose-induced cytotoxicity and radiosensitization in tumor cells is mediated via disruptions in thiol metabolism. Cancer Research, 63(12), 3413–3417.

    CAS  PubMed  Google Scholar 

  24. Rashid, A., Liu, C., Sanli, T., Tsiani, E., Singh, G., Bristow, R. G., et al. (2011). Resveratrol enhances prostate cancer cell response to ionizing radiation. Modulation of the AMPK, Akt and mTOR pathways. Radiation Oncology, 26, 6–144.

    Google Scholar 

  25. Raffoul, J. J., Sarkar, F. H., & Hillman, G. G. (2007). Radiosensitization of prostate cancer by soy isoflavones. Current Cancer Drug Targets, 7(8), 759–765.

    Article  CAS  PubMed  Google Scholar 

  26. Leichman, L. P., Goldman, B. H., & Bohanes, P. O. (2011). S0356: A phase II clinical and prospective molecular trial with oxaliplatin, fluorouracil, and external-beam radiation therapy before surgery for patients with esophageal adenocarcinoma. Journal of Clinical Oncology, 29(34), 4555–4560.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Howes, R. M. (2009). Dangers of antioxidants in cancer patients: A review. Philica. Article ID 153.

  28. Constantinou, C., Papas, A., & Constantinou, A. I. (2008). Vitamin E and cancer: An insight into the anticancer activities of vitamin E isomers and analogs. International Journal of Cancer, 123(4), 739–752.

    Article  CAS  Google Scholar 

  29. Ahles, T. A., & Saykin, A. J. (2007). Candidate mechanisms for chemotherapy-induced cognitive changes. Nature Reviews Cancer, 7(3), 192–201.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Loprinzi, C. L., Barton, D. L., & Jatoi, A. (2007). Symptom control trials: A 20-year experience. Journal of Supportive Oncology, 5(3), 119–128.

    PubMed  Google Scholar 

  31. Nicolson, G. L. (2005). Lipid replacement/antioxidant therapy as an adjunct supplement to reduce the adverse effects of cancer therapy and restore mitochondrial function. Pathology and Oncology Research, 11(3), 139–144.

    Article  CAS  PubMed  Google Scholar 

  32. Osiecki, H. (2002). Cancer: A nutritional, biochemical approach. Eagle Farm, QLD: Bioconcepts Publishing.

    Google Scholar 

  33. Johnstone, R. W., Ruefli, A. A., & Lowe, S. W. (2002). Apoptosis: A link between cancer genetics and chemotherapy. Cell, 108(2), 153–164.

    Article  CAS  PubMed  Google Scholar 

  34. Sagar, S. M., Yance, D., & Wong, R. K. (2006). Natural health product that inhibit angiogenesis: A potential source for investigational new agents to treat cancer—Part 2. Current Oncology, 13(3), 99–107.

    CAS  PubMed Central  PubMed  Google Scholar 

  35. Bansal, T., Jaggi, M., Khar, R. K., & Talegaonkar, S. (2009). Emerging significance of flavonoids as P-glycoprotein inhibitors in cancer chemotherapy. Journal of Pharmacy and Pharmaceutical Sciences, 12(1), 46–78.

    CAS  PubMed  Google Scholar 

  36. Watjen, W., Michels, G., & Steffan, B. (2005). Low concentrations of flavonoids are protective in rat H4IIE cells whereas high concentrations cause DNA damage and apoptosis. Journal of Nutrition, 135(3), 525–531.

    PubMed  Google Scholar 

  37. Lamson, D. W., & Brignall, M. S. (2000). Antioxidants and cancer III: Quercetin. Alternative Medicine Review, 5(3), 196–208.

    CAS  PubMed  Google Scholar 

  38. Lamson, D. W., & Brignall, M. S. (1999). Antioxidants in cancer therapy; their actions and interactions with oncologic therapies. Alternative Medicine Review, 4(5), 304–329.

    CAS  PubMed  Google Scholar 

  39. Davis, S. D. (2007). Nutritional interactions: Credentialing of molecular targets for cancer prevention. Experimental Biology and Medicine, 232(2), 176–183.

    CAS  PubMed  Google Scholar 

  40. Zhang, L., Gu, F. X., Chan, J. M., Wang, A. Z., Langer, R. S., & Farokhzad, O. C. (2008). Nanoparticles in medicine: Therapeutic applications and developments. Clinical Pharmacology Therapy, 83(5), 761–769.

    Article  CAS  Google Scholar 

  41. Northfelt, D. W., Dezube, B. J., & Thommes, J. A. (1998). PEGylated-liposomal doxorubicin versus doxorubicin, bleomycin and vincristine in the treatment of AIDS-related Kaposi’s sarcoma: Results of a randomized phase III clinical trial. Journal of Clinical Oncology, 16(7), 2445–2451.

    CAS  PubMed  Google Scholar 

  42. Harries, M., Ellis, P., & Harper, P. (2005). Nanoparticle albumin-bound paclitaxel for metastatic breast cancer. Journal of Clinical Oncology, 23(31), 7768–7771.

    Article  CAS  PubMed  Google Scholar 

  43. Greco, F., & Vicent, M. J. (2009). Combination therapy: Opportunities and challenges for polymer–drug conjugates as anticancer nanomedicines. Advanced Drug Delivery Reviews, 61(13), 1203–1213.

    Article  CAS  PubMed  Google Scholar 

  44. Agrawal, V., Paul, M. K., & Mukhopadhyay, A. K. (2005). 6-Mercaptopurine and daunorubicin double drug liposomes-preparation, drug–drug interaction and characterization. Journal of Liposome Research, 15(3–4), 141–155.

    Article  CAS  PubMed  Google Scholar 

  45. Saad, M., Garbuzenko, O. B., & Minko, T. (2008). Co-delivery of siRNA and an anticancer drug for treatment of multidrug-resistant cancer. Nanomedicine, 3(6), 761–776.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  46. Bazile, D., Prud’homme, C., Bassoullet, M. T., Marlard, M., Spenlehauer, G., & Veillard, M. (1995). Stealth Me.PEG–PLA nanoparticles avoid uptake by the mononuclear phagocyte system. Journal of Pharmaceutical Sciences, 84(4), 493–498.

    Article  CAS  PubMed  Google Scholar 

  47. Tekade, R. K., Dutta, T., Gajbhiye, V., & Jain, N. K. (2009). Exploring dendrimer towards dual drug delivery: pH responsive simultaneous drug-release kinetics. Journal of Microencapsulation, 26(4), 287–296.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. The First Affiliated Hospital of Yangtze University, No. 8, Hangkong Road, Jingzhou, Hubei, People’s Republic of China

    Lan Chen

  2. Department of Biophysics, Post Graduate Institute of Medical Education and Research, Room No. 525, Research Block B, Chandigarh, 160012, India

    Anshoo Malhotra

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  1. Lan Chen
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Correspondence to Anshoo Malhotra.

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Chen, L., Malhotra, A. Combination Approach: the Future of the War Against Cancer. Cell Biochem Biophys 72, 637–641 (2015). https://doi.org/10.1007/s12013-015-0549-0

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