J Korean Med Assoc.  2015 Nov;58(11):1021-1026. 10.5124/jkma.2015.58.11.1021.

Personalized cancer medicine: present status and future perspectives

• Heo DS

• KMID: 2195131
• DOI: http://doi.org/10.5124/jkma.2015.58.11.1021

Abstract

Most cancers have oncogenes and tumor suppressor genes. First successful drug targeting a oncogene is imatinib. It was very effective for chronic myelogenous leukemia as well as gastrointestinal stromal tumors. Many other targeted agents showed good response: trastuzumab for breast cancer, epidermal growth factor receptor tyrosine kinase inhibitors for non-small cell lung cancer, etc. Tests for EGFR and ALK gene mutation are routinely recommended for adenocarcinoma of lung cancer for selection of anticancer treatment. In addition, large-scale genomic data generation (next generation sequencing) is feasible in a clinical setting and gives us high hope for personalized cancer medicine. However, there are many hurdles to overcome. Driver genes must be distinguished from the passenger genes that are present in tumor DNA. In case of targeted cancer therapy, emergence of drug resistance due to tumor cell heterogeneity and clonal evolution is difficult to manage. Genetic testing for cancer risk showed some success in preventing familial breast or ovarian cancers, but it cannot be generalized in other tumors. Application of genetic information in cancer medicine showed promise but evidence-based approach is needed in clinical practice.

Keyword

Cancer; Precision medicine; Next generation sequencing; Oncogenes; Targeted agents

MeSH Terms

Adenocarcinoma
Breast
Breast Neoplasms
Carcinoma, Non-Small-Cell Lung
Clonal Evolution
DNA
Drug Delivery Systems
Drug Resistance
Gastrointestinal Stromal Tumors
Genes, Tumor Suppressor
Genetic Testing
Hope
Humans
Imatinib Mesylate
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Lung Neoplasms
Oncogenes
Ovarian Neoplasms
Population Characteristics
Protein-Tyrosine Kinases
Receptor, Epidermal Growth Factor
Trastuzumab
DNA
Protein-Tyrosine Kinases
Receptor, Epidermal Growth Factor

Reference

1. Collins FS, Varmus H. A new initiative on precision medicine. N Engl J Med. 2015; 372:793–795.

2. Mukherjee S. The emperor of all maladies: a biography of cancer. London: Fourth Estate;2011.

3. Mendelsohn J. Personalizing oncology: perspectives and prospects. J Clin Oncol. 2013; 31:1904–1911.

4. National Cancer Institute. SEER stat fact sheets: chronic myeloid leukemia (CML) [Internet]. Bethesda, MD: National Cancer Institute;cited 2015 Aug 23. http://seer.cancer.gov/statfacts/html/cmyl.html.

5. National Cancer Institute. Targeted cancer therapies [Internet]. Bethesda, MD: National Cancer Institute;cited 2015 Aug 23. http://www.cancer.gov/cancertopics/treatment/types/targeted-therapies/targeted-therapies-fact-sheet.

6. American Society of Clinical Oncology. What is personalized cancer medicine? [Internet]. Alexandria, VA: American Society of Clinical Oncology;2015. cited 2015 Aug 23. http://www.cancer.net/navigating-cancer-care/how-cancer-treated/personalized-and-targeted-therapies/what-personalized-cancer-medicine.

7. Tirelli U, Berretta M, Bearz A, Carbone A. Grouping of molecularly targeted anti-cancer agents based on cost-effectiveness analysis. Eur Rev Med Pharmacol Sci. 2011; 15:1355–1356.

8. Kolata G. In treatment for leukemia, glimpse of the future [Internet]. New York: New York Times;2012. cited 2015 Aug 23. http://www.nytimes.com/2012/07/08/health/in-gene-sequencing-treatment-for-leukemia-glimpses-of-the-future.html?_r=0.

9. Kabir NN, Ronnstrand L, Kazi JU. FLT3 mutations in patients with childhood acute lymphoblastic leukemia (ALL). Med Oncol. 2013; 30:462.

10. American Society of Clinical Oncology. Understanding pharmacogenomics [Internet]. Alexandria, VA: American Society of Clinical Oncology;2015. cited 2015 Aug 23. Available from: http://www.cancer.net/navigating-cancer-care/how-cancer-treated/personalized-and-targeted-therapies/understanding-pharmacogenomics.

11. Song SC. Half of BRCA1 carriers develop breast cancer. [Internet]. Seoul: Doctor's News;2015. cited 2015 Aug 23. http://www.doctorsnews.co.kr/news/articleView.html?idxno=105354.

12. Zhao Y, Adjei AA. Targeting oncogenic drivers. Prog Tumor Res. 2014; 41:1–14.

13. Suda K, Mitsudomi T. Successes and limitations of targeted cancer therapy in lung cancer. Prog Tumor Res. 2014; 41:62–77.

14. Welch HG, Schwartz L, Woloshin S. Overdiagnosed: making people sick in the pursuit of health. Boston, MA: Beacon Press;2011.

15. Dienstmann R, Rodon J, Barretina J, Tabernero J. Genomic medicine frontier in human solid tumors: prospects and challenges. J Clin Oncol. 2013; 31:1874–1884.

16. Fojo T, Grady C. How much is life worth: cetuximab, non-small cell lung cancer, and the $440 billion question. J Natl Cancer Inst. 2009; 101:1044–1048.

17. American Society of Clinical Oncology. ASCO in Action Brief: value in cancer care [Internet]. Alexandria, VA: American Society of Clinical Oncology;2014. cited 2015 Oct 28. Available from: http://www.asco.org/advocacy/asco-action-brief-value-cancer-care.

18. Rubin MA. Health: Make precision medicine work for cancer care. Nature. 2015; 520:290–291.

19. Garraway LA, Verweij J, Ballman KV. Precision oncology: an overview. J Clin Oncol. 2013; 31:1803–1805.