Skip to main content

The Missing Components Today and the New Treatments Tomorrow

  • Chapter
  • First Online:
Book cover Cancer Targeted Drug Delivery

Abstract

The history of drug delivery technology is only 60 years old, but various mechanisms of controlled drug delivery have been well established. While numerous controlled release formulations have been developed, only a handful of these approaches has been used successfully as anticancer treatments. Current approaches to deliver anticancer agents to tumors commonly involve the intravenous administration of submicron size formulations. These nanoparticle-based approaches frequently show impressive efficacy in small animal tumor models, but their translation to safe and efficacious clinical outcomes has been disappointing. It is our thesis that the poor success rate of these approaches is primarily due to an insufficient understanding of cancer biology and physiology; knowledge that is necessary to achieve selective and efficient targeting of these anticancer therapies. To substantially improve targeted drug delivery to treat cancers we must know more about how cancer cell heterogeneity, cancer cell drug resistance, as well as tumor properties and microenvironments play a role in cancer development, progression, and metastasis. Additionally, there is a great need to identify in vitro and in vivo models that more directly emulate specific elements of cancer cells and tumors that restrict the success of our current anticancer approaches. Although a complete cure of cancer is the ultimate goal, it may be more realistic in the near future to treat cancer as a chronic disease using improved drugs and better drug delivery systems.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Winau F, Westphal O, Winau R (2004) Paul Ehrlich—in search of the magic bullet. Microbes Infect 6(8):786–789. doi:org/10.1016/j.micinf.2004.04.003

    Article  CAS  PubMed  Google Scholar 

  2. Bae YH, Park K (2011) Targeted drug delivery to tumors: myths, reality, and possibility. J Control Release 153:198–205

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Dokoumetzidis A, Macheras P (2006) A century of dissolution research: from Noyes and Whitney to the biopharmaceutics classification system. Int J Pharm 321(1–2):1–11. doi:org/10.1016/j.ijpharm.2006.07.011

    Article  CAS  PubMed  Google Scholar 

  4. Langer RS, Wise D (eds) (1984) Medical applications of controlled release, vols 2 and 3. CRC, Boca Raton, FL

    Google Scholar 

  5. Hoffman AS (2008) The origins and evolution of “controlled” drug delivery systems. J Control Release 132(3):153–163

    Article  CAS  PubMed  Google Scholar 

  6. Wen H, Park K (eds) (2010) Oral controlled release formulation design and drug delivery: theory to practice. Wiley, New York

    Google Scholar 

  7. Jeong B, Kim SW, Bae YH (2012) Thermosensitive sol–gel reversible hydrogels. Adv Drug Deliv Rev 64(Suppl):154–162. doi:org/10.1016/j.addr.2012.09.012

    Article  Google Scholar 

  8. Jeong SH, Oh KT, Park K (2013) Glucose-sensitive hydrogels. In: Dumitriu S, Popa V (eds) Polymeric biomaterials, vol 2, 3rd edn, Medicinal and pharmaceutical applications of polymers. CRC, Boca Raton, FL, pp 43–64

    Chapter  Google Scholar 

  9. Lammers T, Kiessling F, Hennink WE, Storm G (2012) Drug targeting to tumors: principles, pitfalls and (pre-) clinical progress. J Control Release 161(2):175–187. doi:org/10.1016/j.jconrel.2011.09.063

    Article  CAS  PubMed  Google Scholar 

  10. Kwon IK, Lee SC, Han B, Park K (2012) Analysis on the current status of targeted drug delivery to tumors. J Control Release 164(2):108–114. doi:org/10.1016/j.jconrel.2012.07.010

    Article  CAS  PubMed  Google Scholar 

  11. Nichols JW, Bae YH (2012) Odyssey of a cancer nanoparticle: from injection site to site of action. Nano Today 7(6):606–618. doi:org/10.1016/j.nantod.2012.10.010

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Matsumura Y, Maeda H (1986) A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res 46:6387–6392

    CAS  PubMed  Google Scholar 

  13. Cuomo MI (2012) A world without cancer. The making of a new cure and the real promise of prevention. Rodale, New York

    Google Scholar 

  14. Brock DW (2010) Ethical and value issues in insurance coverage for cancer treatment. Oncologist 15:36–42

    Article  PubMed  Google Scholar 

  15. Beil L (2012) How much would you pay for three more months of life? Newsweek 160(10):40–47

    Google Scholar 

  16. Montesano R, Hall J (2001) Environmental causes of human cancers. Eur J Cancer 37(Suppl 8):67–87. doi:org/10.1016/S0959-8049(01)00266-0

    Article  Google Scholar 

  17. Jiang J, Liu B, Nasca PC, Chen J, Zeng X, Wu Y, Zou X, Zhao P, Li J (2008) Age-related effects of smoking on lung cancer mortality: a nationwide case-control comparison in 103 population centers in china. Ann Epidemiol 18(6):484–491. doi:org/10.1016/j.annepidem.2008.01.004

    Article  PubMed  Google Scholar 

  18. Eyre HJ (2009) Winning the cancer fight: a look at the future. Prim Care 36(4):859–865. doi:org/10.1016/j.pop.2009.07.003

    Article  PubMed  Google Scholar 

  19. Harbeck N, Salem M, Nitz U, Gluz O, Liedtke C (2010) Personalized treatment of early-stage breast cancer: present concepts and future directions. Cancer Treat Rev 36(8):584–594. doi:org/10.1016/j.ctrv.2010.04.007

    Article  PubMed  Google Scholar 

  20. Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA, Gocayne JD, Amanatides P, Ballew RM, Huson DH, Wortman JR, Zhang Q, Kodira CD, Zheng XH, Chen L, Skupski M, Subramanian G, Thomas PD, Zhang J, Gabor Miklos GL, Nelson C, Broder S, Clark AG, Nadeau J, McKusick VA, Zinder N, Levine AJ, Roberts RJ, Simon M, Slayman C, Hunkapiller M, Bolanos R, Delcher A, Dew I, Fasulo D, Flanigan M, Florea L, Halpern A, Hannenhalli S, Kravitz S, Levy S, Mobarry C, Reinert K, Remington K, Abu-Threideh J, Beasley E, Biddick K, Bonazzi V, Brandon R, Cargill M, Chandramouliswaran I, Charlab R, Chaturvedi K, Deng Z, Di Francesco V, Dunn P, Eilbeck K, Evangelista C, Gabrielian AE, Gan W, Ge W, Gong F, Gu Z, Guan P, Heiman TJ, Higgins ME, Ji RR, Ke Z, Ketchum KA, Lai Z, Lei Y, Li Z, Li J, Liang Y, Lin X, Lu F, Merkulov GV, Milshina N, Moore HM, Naik AK, Narayan VA, Neelam B, Nusskern D, Rusch DB, Salzberg S, Shao W, Shue B, Sun J, Wang Z, Wang A, Wang X, Wang J, Wei M, Wides R, Xiao C, Yan C, Yao A, Ye J, Zhan M, Zhang W, Zhang H, Zhao Q, Zheng L, Zhong F, Zhong W, Zhu S, Zhao S, Gilbert D, Baumhueter S, Spier G, Carter C, Cravchik A, Woodage T, Ali F, An H, Awe A, Baldwin D, Baden H, Barnstead M, Barrow I, Beeson K, Busam D, Carver A, Center A, Cheng ML, Curry L, Danaher S, Davenport L, Desilets R, Dietz S, Dodson K, Doup L, Ferriera S, Garg N, Gluecksmann A, Hart B, Haynes J, Haynes C, Heiner C, Hladun S, Hostin D, Houck J, Howland T, Ibegwam C, Johnson J, Kalush F, Kline L, Koduru S, Love A, Mann F, May D, McCawley S, McIntosh T, McMullen I, Moy M, Moy L, Murphy B, Nelson K, Pfannkoch C, Pratts E, Puri V, Qureshi H, Reardon M, Rodriguez R, Rogers YH, Romblad D, Ruhfel B, Scott R, Sitter C, Smallwood M, Stewart E, Strong R, Suh E, Thomas R, Tint NN, Tse S, Vech C, Wang G, Wetter J, Williams S, Williams M, Windsor S, Winn-Deen E, Wolfe K, Zaveri J, Zaveri K, Abril JF, Guigo R, Campbell MJ, Sjolander KV, Karlak B, Kejariwal A, Mi H, Lazareva B, Hatton T, Narechania A, Diemer K, Muruganujan A, Guo N, Sato S, Bafna V, Istrail S, Lippert R, Schwartz R, Walenz B, Yooseph S, Allen D, Basu A, Baxendale J, Blick L, Caminha M, Carnes-Stine J, Caulk P, Chiang YH, Coyne M, Dahlke C, Mays A, Dombroski M, Donnelly M, Ely D, Esparham S, Fosler C, Gire H, Glanowski S, Glasser K, Glodek A, Gorokhov M, Graham K, Gropman B, Harris M, Heil J, Henderson S, Hoover J, Jennings D, Jordan C, Jordan J, Kasha J, Kagan L, Kraft C, Levitsky A, Lewis M, Liu X, Lopez J, Ma D, Majoros W, McDaniel J, Murphy S, Newman M, Nguyen T, Nguyen N, Nodell M, Pan S, Peck J, Peterson M, Rowe W, Sanders R, Scott J, Simpson M, Smith T, Sprague A, Stockwell T, Turner R, Venter E, Wang M, Wen M, Wu D, Wu M, Xia A, Zandieh A, Zhu X (2001) The sequence of the human genome. Science 5507:1304–1351. doi:10.1126/science.1058040

    Article  Google Scholar 

  21. Hobbs SK, Monsky WL, Yuan F, Roberts WG, Griffith L, Torchilin VP, Jain RK (1998) Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment. Proc Natl Acad Sci U S A 95(8):4607–4612

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. McDonald DM, Choyke PL (2003) Imaging angiogenesis: from microscope to clinic. Nat Med 9(6):713–725

    Article  CAS  PubMed  Google Scholar 

  23. Dvorak HF, Nagy JA, Dvorak JT, Dvorak AM (1988) Identification and characterization of the blood vessels of solid tumors that are leaky to circulating macromolecules. Am J Pathol 133(1):95–109

    CAS  PubMed  Google Scholar 

  24. Hanahan D, Weinberg Robert A (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674. doi:org/10.1016/j.cell.2011.02.013

    Article  CAS  PubMed  Google Scholar 

  25. Harrington KJ (2011) Biology of cancer. Medicine 39(12):689–692. doi:org/10.1016/j.mpmed.2011.09.015

    Article  Google Scholar 

  26. Subcommittee-on-Personalized-Medicine (2008) Priorities for personalized medicine. President’s Council of Advisors on Science and Technology, Washington, DC

    Google Scholar 

  27. De Palma M, Hanahan D (2012) The biology of personalized cancer medicine: facing individual complexities underlying hallmark capabilities. Mol Oncol 6(2):111–127. doi:10.1016/j.molonc.2012.01.011

    Article  PubMed  Google Scholar 

  28. Hurvitz SA, Hu Y, O’Brien N, Finn RS (2013) Current approaches and future directions in the treatment of her2-positive breast cancer. Cancer Treat Rev 39(3):219–229. doi:org/10.1016/j.ctrv.2012.04.008

    Article  CAS  PubMed  Google Scholar 

  29. Pliarchopoulou K, Pectasides D (2009) Pancreatic cancer: current and future treatment strategies. Cancer Treat Rev 35(5):431–436. doi:org/10.1016/j.ctrv.2012.04.008

    Article  CAS  PubMed  Google Scholar 

  30. Pokrzywinski R, Secord AA, Havrilesky LJ, Puls LE, Holloway RW, Lewandowski GS, Higgins RV, Nycum LR, Kohler MF, Revicki DA (2011) Health-related quality of life outcomes of docetaxel/carboplatin combination therapy vs. sequential therapy with docetaxel then carboplatin in patients with relapsed, platinum-sensitive ovarian cancer: results from a randomized clinical trial. Gynecol Oncol 123(3):505–510. doi:10.1016/j.ygyno.2011.08.015

    Article  CAS  PubMed  Google Scholar 

  31. Shah U, Goldberg RM (2009) Sequential versus combination therapy in the treatment of patients with advanced colorectal cancer. Clin Colorectal Cancer 8(Suppl):17–22. doi:10.1016/s1533-0028(11)70552-7

    Article  Google Scholar 

  32. Shao N, Wang S, Yao C, Xu X, Zhang Y, Zhang Y, Lin Y (2012) Sequential versus concurrent anthracyclines and taxanes as adjuvant chemotherapy of early breast cancer: a meta-analysis of phase III randomized control trials. Breast 21(3):389–393. doi:10.1016/j.breast.2012.03.011

    Article  PubMed  Google Scholar 

  33. Vriens BEPJ, Lobbezoo DJA, de Hoon JPJ, Veeck J, Voogd AC, Tjan-Heijnen VCG (2013) If there is no overall survival benefit in metastatic breast cancer: does it imply lack of efficacy? Taxanes as an example. Cancer Treat Rev 39(2):189–198. doi:10.1016/j.ctrv.2012.04.005

    Article  PubMed  Google Scholar 

  34. Tkaczuk KHR (2009) Review of the contemporary cytotoxic and biologic combinations available for the treatment of metastatic breast cancer. Clin Ther 31(Pt 2):2273–2289. doi:10.1016/j.clinthera.2009.11.011

    Article  PubMed  Google Scholar 

  35. Hamberg P, Bos MMEM, Braun HJJ, Stouthard JML, van Deijk GA, Erdkamp FLG, van der Stelt-Frissen IN, Bontenbal M, Creemers G-JM, Portielje JEA, Pruijt JFM, Loosveld OJL, Smit WM, Muller EW, Schmitz PIM, Seynaeve C, Klijn JGM (2011) Randomized phase II study comparing efficacy and safety of combination-therapy trastuzumab and docetaxel vs. sequential therapy of trastuzumab followed by docetaxel alone at progression as first-line chemotherapy in patients with her2+ metastatic breast cancer: Hertax trial. Clin Breast Cancer 11(2):103–113. doi:10.1016/j.clbc.2011.03.003

    Article  CAS  PubMed  Google Scholar 

  36. Cortes J, Roché H (2012) Docetaxel combined with targeted therapies in metastatic breast cancer. Cancer Treat Rev 38(5):387–396. doi:10.1016/j.ctrv.2011.08.001

    Article  CAS  PubMed  Google Scholar 

  37. Kola I, Landis J (2004) Can the pharmaceutical industry reduce attrition rates? Nat Rev Drug Discov 3(8):711–715

    Article  CAS  PubMed  Google Scholar 

  38. Kamb A (2005) The mighty mouse: genetically engineered mouse models in cancer drug development. Nat Rev Drug Discov 4(2):161–165

    Article  CAS  PubMed  Google Scholar 

  39. Sharpless NE, Depinho RA (2006) The mighty mouse: genetically engineered mouse models in cancer drug development. Nat Rev Drug Discov 5(9):741–754

    Article  CAS  PubMed  Google Scholar 

  40. Erkan M, Hausmann S, Michalski CW, Fingerle AA, Dobritz M, Kleeff J, Friess H (2012) The role of stroma in pancreatic cancer: diagnostic and therapeutic implications. Nat Rev Gastroenterol Hepatol 9(8):454–467. doi:10.1038/nrgastro.2012.115

    Article  CAS  PubMed  Google Scholar 

  41. Herreros-Villanueva M, Hijona E, Cosme A, Bujanda L (2012) Mouse models of pancreatic cancer. World J Gastroenterol 18(12):1286–1294. doi:10.3748/wjg.v18.i12.1286

    Article  PubMed  Google Scholar 

  42. Jacobetz MA, Chan DS, Neesse A, Bapiro TE, Cook N, Frese KK, Feig C, Nakagawa T, Caldwell ME, Zecchini HI, Lolkema MP, Jiang P, Kultti A, Thompson CB, Maneval DC, Jodrell DI, Frost GI, Shepard HM, Skepper JN, Tuveson DA (2013) Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer. Gut 62(1):112–120. doi:10.1136/gutjnl-2012-302529

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Gidekel Friedlander SY, Chu GC, Snyder EL, Girnius N, Dibelius G, Crowley D, Vasile E, DePinho RA, Jacks T (2009) Context-dependent transformation of adult pancreatic cells by oncogenic k-ras. Cancer Cell 16(5):379–389. doi:10.1016/j.ccr.2009.09.027

    Article  PubMed Central  PubMed  Google Scholar 

  44. Acharyya S, Oskarsson T, Vanharanta S, Malladi S, Kim J, Morris PG, Manova-Todorova K, Leversha M, Hogg N, Seshan VE, Norton L, Brogi E, Massague J (2012) A cxcl1 paracrine network links cancer chemoresistance and metastasis. Cell 150(1):165–178. doi:10.1016/j.cell.2012.04.042

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Robbins PF, Morgan RA, Feldman SA, Yang JC, Sherry RM, Dudley ME, Wunderlich JR, Nahvi AV, Helman LJ, Mackall CL, Kammula US, Hughes MS, Restifo NP, Raffeld M, Lee CC, Levy CL, Li YF, El-Gamil M, Schwarz SL, Laurencot C, Rosenberg SA (2011) Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with ny-eso-1. J Clin Oncol 29(7):917–924. doi:10.1200/JCO.2010.32.2537

    Article  PubMed  Google Scholar 

  46. Madan RA, Gulley JL (2011) Sipuleucel-t: harbinger of a new age of therapeutics for prostate cancer. Expert Rev Vaccines 10(2):141–150. doi:10.1586/erv.10.173

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Eastwood D, Findlay L, Poole S, Bird C, Wadhwa M, Moore M, Burns C, Thorpe R, Stebbings R (2010) Monoclonal antibody tgn1412 trial failure explained by species differences in cd28 expression on cd4+ effector memory t-cells. Br J Pharmacol 161(3):512–526. doi:10.1111/j.1476-5381.2010.00922.x

    Article  CAS  PubMed  Google Scholar 

  48. Grosso JF, Jure-Kunkel MN (2013) Ctla-4 blockade in tumor models: an overview of preclinical and translational research. Cancer Immun 13:5

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Park, K., Bae, Y.H., Mrsny, R.J. (2013). The Missing Components Today and the New Treatments Tomorrow. In: Bae, Y., Mrsny, R., Park, K. (eds) Cancer Targeted Drug Delivery. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7876-8_26

Download citation

Publish with us

Policies and ethics