Making a difference with teamwork

Introduction

Making a difference with teamwork


V. Hirsh , MD


Lung cancer is the leading cause of cancer-related mortality in Canada 1. The American Cancer Society estimated that, in 2011, more than 200,000 patients would be newly diagnosed with lung cancer and that more than 150,000 would die of the disease. Non-small-cell lung cancer ( nsclc ) is the most common form of lung cancer, accounting for approximately 87% of cases 2,3.

Systemic chemotherapies, especially platinum-based doublets, have been used to treat nsclc for several decades, but improvements in outcomes have reached a plateau 4,5. When platinum-based doublets are administered for advanced nsclc , median survival improves to 8–10 months (from 4–5 months without treatment). Significant toxicities limit the number of cycles that can be administered 6.

Current algorithms for first-line treatment of advanced nsclc recommend using both histologic and molecular diagnostics in designing the course of treatment 7. Recent advances in understanding signalling pathways for malignant cells, interconnections in those pathways, the importance of various receptors and biomarkers, and the interplay between various oncogenes have led to the development of targeted treatments that are improving not only efficacy benefits, but also safety benefits. These treatments are aimed at specific—especially genetic—changes in the malignant cells. Various nsclc subtypes are associated with potentially targetable biomarkers such as mutation of the epidermal growth factor receptor ( EGFR ) 812, KRAS 13, echinoderm microtubule-associated protein-like 4 ( EML4 ), and anaplastic lymphoma kinase ( ALK ) genes or the presence of fusion genes ( EML4–ALK ) 14,15 and c-Met overexpression or amplification 1619.

Knowledge about the advantages of treatments with targeted agents in advanced nsclc is growing, but the hope is eventually to apply that knowledge to earlier stages of nsclc and thus to increase the cure rate. Combining various targeted agents or sequencing them properly will be of the utmost importance in the new era of targeted personalized therapy.

In this supplement of Current Oncology, contributors describe the importance of teamwork from diagnosis through various treatments to supportive care, and from interventional procedures (in which satisfactory tumour specimens must be obtained for analyses by pathologists and molecular biologists) to treatments delivered by radiation oncologists, medical oncologists, and supportive care specialists. In addition, descriptions of ongoing clinical trials provide a glimpse of the future. The result is, we hope, a complete review of present and future approaches to personalized medicine in advanced nsclc in Canada.

REFERENCES

1.  Canadian Cancer Society’s Steering Committee. Canadian Cancer Statistics 2010. Toronto: Canadian Cancer Society; 2010.

2.  United States, National Institutes of Health, National Cancer Institute ( nci ). Non-small cell lung cancer treatment (PDQ). Health professional version [Web page]. Bethesda, MD: nci ; n.d. [Available online at: http://www.cancer.gov/cancertopics/pdq/treatment/non-small-cell-lung/healthprofessional; cited September 12, 2010]

3.  Pisters KM, Evans WK, Azzoli CG, et al. Cancer Care Ontario and American Society of Clinical Oncology adjuvant chemotherapy and adjuvant radiation therapy for stages i iiia resectable non small-cell lung cancer guideline. J Clin Oncol 2007;25:5506–18.
cross-ref  pubmed  

4.  Cagle PT, Allen TC, Dacic S, et al. Revolution in lung cancer: new challenges for the surgical pathologist. Arch Pathol Lab Med 2011;135:110–16.
pubmed  

5.  Schiller JH, Harrington D, Belani CP, et al. on behalf of the Eastern Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 2002;346:92–8.
cross-ref  pubmed  

6.  Cagle PT, Dacic S. Lung cancer and the future of pathology. Arch Pathol Lab Med 2011;135:293–5.
pubmed  

7.  Scagliotti GV, Parikh P, von Pawel J, et al. Phase iii study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol 2008;26:3543–51.
cross-ref  pubmed  

8.  Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004;350:2129–39.
cross-ref  pubmed  

9.  Paez JG, Jänne PA, Lee JC, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004;304:1497–500.
cross-ref  pubmed  

10.  Pao W, Miller V, Zakowski M, et al. egf receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci U S A 2004;101:13306–11.
cross-ref  pubmed  

11.  Li AR, Chitale D, Riely GJ, et al. EGFR mutations in lung adenocarcinomas: clinical testing experience and relationship to EGFR gene copy number and immunohistochemical expression. J Mol Diagn 2008;10:242–8.
cross-ref  pubmed  

12.  Uramoto H, Mitsudomi T. Which biomarker predicts benefit from egfr - tki treatment for patients with lung cancer? Br J Cancer 2007;96:857–63.
cross-ref  pubmed  

13.  Sartori G, Cavazza A, Sgambato A, et al. EGFR and K- ras mutations along the spectrum of pulmonary epithelial tumors of the lung and elaboration of a combined clinicopathologic and molecular scoring system to predict clinical responsiveness to egfr inhibitors. Am J Clin Pathol 2009;131:478–89.
cross-ref  pubmed  

14.  Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancer. Nature 2007;448:561–6.
cross-ref  pubmed  

15.  Wong DW, Leung EL, So KK, et al. The EML4–ALK fusion gene is involved in various histologic types of lung cancers from nonsmokers with wild-type EGFR and KRAS. Cancer 2009;115:1723–33.
cross-ref  pubmed  

16.  Ma PC, Tretiakova MS, MacKinnon AC, et al. Expression and mutational analysis of MET in human solid cancers. Genes Chromosomes Cancer 2008;47:1025–37.
cross-ref  pubmed  

17.  Okuda K, Sasaki H, Yukiue H, Yano M, Fujii Y. MET gene copy number predicts the prognosis for completely resected non-small cell lung cancer. Cancer Sci 2008;99:2280–5.
cross-ref  pubmed  

18.  Lutterbach B, Zeng Q, Davis LJ, et al. Lung cancer cell lines harboring MET gene amplification are dependent on Met for growth and survival. Cancer Res 2007;67:2081–8. [Erratum in: Cancer Res 2007;67:3987]
cross-ref  pubmed  

19.  Engelman JA, Zejnullahu K, Mitsudomi T, et al. MET amplification leads to gefitinib resistance in lung cancer by activating ErbB3 signaling. Science 2007;316:1039–43.
cross-ref  pubmed  


(Return to Top)


The publication of this supplement was made possible through unrestricted grants from Boehringer Ingelheim, Hoffmann–La Roche, and Pfizer. We sincerely thank them for having accepted to help support this project and for their commitment to research and education in lung cancer.


Current Oncology , VOLUME 19 , NUMBER Supplement 1 , 2012








Copyright © 2019 Multimed Inc.
ISSN: 1198-0052 (Print) ISSN: 1718-7729 (Online)