Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Clinical cancer research: the past, present and the future

Abstract

In the past decade, we have witnessed unprecedented changes and some remarkable advances that have enabled true personalized medicine. Nevertheless, many challenges in clinical cancer research remain and need to be overcome if we are to witness similar progress in the next decade. Such hurdles include, but are not limited to, clinical development and testing of multiple agents in combination, design of clinical trials to best accommodate the ever increasing knowledge of heterogeneity of the disease, regulatory challenges relating to drug development and trial design, and funding for basic research. With this in mind, we asked four leading cancer researchers from around the world, and who have been associated with the journal since its launch in November 2004 what, in their opinion, we have learnt over the past 10 years and how we should progress in the next 10 years.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Kochenderfer, J. N. et al. Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. Blood 116, 4099–4102 (2010).

    CAS  Article  Google Scholar 

  2. 2

    Tran, E. et al. Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer. Science 344, 641–645 (2014).

    CAS  Article  Google Scholar 

  3. 3

    Simeone, E. & Ascierto, P. A. Immunomodulating antibodies in the treatment of metastatic melanoma: the experience with anti-CTLA-4, anti-CD137 and anti-PD1. J. Immunotoxicol. 9, 241–247 (2012).

    CAS  Article  Google Scholar 

  4. 4

    Ascierto, P. A. et al. Clinical experiences with anti-CD137 and anti-PD1 therapeutic antibodies. Semin. Oncol. 37, 508–516 (2010).

    CAS  Article  Google Scholar 

  5. 5

    Flaherty, K. T., Puzanov, I. & Chapman, P. B. Inhibition of mutated, activated BRAF in metastatic melanoma. N. Engl. J. Med. 363, 809–819 (2010).

    CAS  Article  Google Scholar 

  6. 6

    Lynch, T. J. et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness on non-small-cell lung cancer to gefitinib. N. Engl. J. Med. 350, 2129–2139 (2004).

    CAS  Article  Google Scholar 

  7. 7

    Shaw, A. T. et al. Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis. Lancet Oncol. 12, 1004–1012 (2011).

    CAS  Article  Google Scholar 

  8. 8

    Eggermont, A. M., Spatz, A. & Robert, C. Cutaneous melanoma. Lancet 383, 816–827 (2014).

    CAS  Article  Google Scholar 

  9. 9

    Hodi, F. S. et al. Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med. 363, 711–723 (2010).

    CAS  Article  Google Scholar 

  10. 10

    Topalian, S. L. et al. Survival, durable tumour remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J. Clin. Oncol. 32, 1020–1030 (2014).

    CAS  Article  Google Scholar 

  11. 11

    Robert, C. et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet http://dx.doi.org/10.1016/S0140-6736(14)60958-2 (2014).

  12. 12

    Brahmer, J. R. et al. Survival and long-term follow-up of the phase I trial of nivolumab (anti-PD-1; BMS-936558; ONO-4538) in patients (pts) with previously treated advanced non-small cell lung cancer (NSCLC) [abstract]. J. Clin. Oncol. 31 (Suppl.), a8030 (2013).

    Google Scholar 

  13. 13

    Powles, T. et al. Inhibition of PD-L1 by MPDL3280A and clinical activity in pts with metastatic urothelial bladder cancer (UBC) [abstract]. J. Clin. Oncol. 32 (Suppl.), a5011 (2014).

    Article  Google Scholar 

  14. 14

    Wolchok, J. D. et al. Nivolumab plus ipilimumab in advanced melanoma. N. Engl. J. Med. 369, 122–133 (2013).

    CAS  Article  Google Scholar 

  15. 15

    Eggermont, A. M. & Robert, C. Melanoma: smart therapeutic strategies in immuno-oncology. Nat. Rev. Clin. Oncol. 11, 181–182 (2014).

    CAS  Article  Google Scholar 

  16. 16

    Peggs, K. S., Quezada, S. A., Chambers, C. A., Korman, A. J. & Allison, J. P. Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumour activity of anti-CTLA-4 antibodies. J. Exp. Med. 206, 1717–1725 (2009).

    CAS  Article  Google Scholar 

  17. 17

    Kraman, M. et al. Suppression of antitumour immunity by stromal cells expressing fibroblast activation protein-alpha. Science 330, 827–830 (2010).

    CAS  Article  Google Scholar 

  18. 18

    Wolchok, J. D. et al. Nivolumab plus ipilimumab in advanced melanoma. N. Engl. J. Med. 369, 122–133 (2013).

    CAS  Article  Google Scholar 

  19. 19

    Hinrichs, C. S. & Rosenberg, S. A. Exploiting the curative potential of adoptive T-cell therapy for cancer. Immunol. Rev. 257, 56–71 (2014).

    CAS  Article  Google Scholar 

  20. 20

    Lee, Y. et al. Therapeutic effects of ablative radiation on local tumour require CD8+ T cells: changing strategies for cancer treatment. Blood 114, 589–595 (2009).

    CAS  Article  Google Scholar 

  21. 21

    Garcia-Barros, M. et al. Tumour response to radiotherapy regulated by endothelial cell apoptosis. Science 300, 1155–1159 (2003).

    CAS  Article  Google Scholar 

  22. 22

    Lussier, Y. A. et al. Oligo and polymetastatic progression in lung metastasis(es) patients is associated with specific microRNAs. PLoS ONE 7, e50141 (2012).

    CAS  Article  Google Scholar 

  23. 23

    La Thangue, N. B. & Kerr, D. J. Predictive biomarkers: a shift towards personalised cancer medicine. Nat. Rev. Clin. Oncol. 8, 587–596 (2011).

    CAS  Article  Google Scholar 

  24. 24

    Kerr, D. J. & Kakil, I. R. Targeted therapies: cetuximab plus chemotherapy in patients with advanced cancer. Nat. Rev. Clin. Oncol. 6, 499–500 (2009).

    Article  Google Scholar 

  25. 25

    Ou, S.-H. I. et al. Efficacy and safety of crizotinib in patients with advanced ROS1-rearranged non-small cell lung cancer (NSCLC) [abstract]. J. Clin. Oncol. 31 (Suppl.), a8032 (2013).

    Google Scholar 

  26. 26

    Dilts, D. M. et al. Development of clinical trials in a cooperative group setting: The Eastern Cooperative Oncology Group. Clin. Cancer Res. 14, 3427–3433 (2008).

    Article  Google Scholar 

  27. 27

    Lacombe, D. et al. European perspective for effective cancer drug development. Nat. Rev. Clin. Oncol. 11, 492–498 (2014).

    Article  Google Scholar 

  28. 28

    Edwards, A. M., Bountra, C., Kerr, D. J. & Willson, T. M. Open access chemical and clinical probes to support drug discovery. Nat. Chem. Biol. 5, 436–440 (2009).

    CAS  Article  Google Scholar 

  29. 29

    Prahallad, A. et al. Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature 483, 100–103 (2012).

    CAS  Article  Google Scholar 

  30. 30

    Ward, P. S. & Thompson, C. B. Metabolic reprogramming: a cancer hallmark even warburg did not anticipate. Cancer Cell 21, 297–308 (2012).

    CAS  Article  Google Scholar 

  31. 31

    Heimann, R. & Hellman, S. Clinical progression of breast cancer malignant behaviour: what to expect and when to expect it. J. Clin. Oncol. 18, 591–599 (2000).

    CAS  Article  Google Scholar 

  32. 32

    Coussens, L. & Werb, Z. Inflammation and cancer. Nature 420, 860–867 (2002).

    CAS  Article  Google Scholar 

  33. 33

    Cogent Study Group. Meta-analysis of genome-wide association data identifies four new susceptibility loci for colorectal cancer. Nat. Genet. 40, 1426–1435 (2008).

  34. 34

    Liao, M. et al. Aspirin use, PIK3C mutation and colorectal cancer survival. N. Engl. J. Med. 367, 1596–1606 (2012).

    CAS  Article  Google Scholar 

  35. 35

    Domingo, E. et al. Evaluation of PIK3CA mutation as a predictor of benefit from nonsteroidal anti-inflammatory drug therapy in colorectal cancer. J. Clin. Oncol. 31, 4297–4305 (2013).

    CAS  Article  Google Scholar 

  36. 36

    Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell 144, 646–674 (2011).

    CAS  Article  Google Scholar 

  37. 37

    Hanahan, D. & Weinberg, R. A. Hallmarks of Cancer: an organizing principle for cancer medicine. Cancer: Principles & Practice of Oncology. 10th edn, Ch. 2 (in press, November 2014).

    Google Scholar 

  38. 38

    Dunn, G. P., Old, L. J. & Schreiber, R. D. The three Es of cancer immunoediting. Annu. Rev. Immunol. 22, 329–360 (2004).

    CAS  Article  Google Scholar 

  39. 39

    Grey, R. et al. Validation study of a quantitative multi-gene RT-PCR assay as a predictor of recurrence in stage II colon cancer patient. J. Clin. Oncol. 12, 4611–4619 (2011).

    Article  Google Scholar 

  40. 40

    Church, D. et al. Toxgnostics: an unmet need in cancer medicine. Nat. Rev. Cancer 14, 440–445 (2014).

    CAS  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding authors

Correspondence to Vincent T. DeVita Jr or Alexander M. M. Eggermont or Samuel Hellman or David J. Kerr.

Ethics declarations

Competing interests

A.M.M.E. is on the scientific advisory board and receives honoraria from Bristol–Myers Squibb and Merck Sharp & Dohme Limited. D.J.K. is Director of the Oxford University spin out company, Oxford Cancer Biomarkers. The other authors declare no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

DeVita, V., Eggermont, A., Hellman, S. et al. Clinical cancer research: the past, present and the future. Nat Rev Clin Oncol 11, 663–669 (2014). https://doi.org/10.1038/nrclinonc.2014.153

Download citation

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing