Genetic mutations and lung cancer
Each protein in the body is made according to the instructions encoded in a gene. Sometimes there’s an error in these instructions that causes the protein to work differently to how it should– this is a mutation.1,2 Not all mutations cause cancer, but mutations are often associated with cancer, and the growth of cancer cells is sometimes triggered by underlying mutations.3
Scientists suspect that most cancers are the result of a combination of mutations. But there are some “driver mutations” that are important in the start and spread of cancer. Just one may be enough to initiate tumour growth.1,2
Common genetic mutations in lung cancer and potential therapies
We are now in an era of increasing genetic knowledge and the treatment options and outcomes for a subset of patients with lung cancer are improving. One of the reasons for this is the development of a number of targeted therapies, which inhibit the particular molecules or pathways on which an individual tumour relies on in order to survive, grow and spread.2,4 Identification of groups of cancers that are predicted to respond to targeted treatments highlights the potential for a more personalised approach to cancer care.
A biopsy or plasma ctDNA test helps physicians learn about the genetic makeup of cancer cells through a process called molecular testing.5,6 These tests can show which genetic mutations are present in the cancer cells of someone with cancer. Patients who might benefit from available targeted therapies can thus be identified.
Examples of targetable genetic mutations that have already been identified include EGFR (epidermal growth factor receptor),7 ALK (anaplastic lymphoma kinase),8 KRAS (Kirsten rat sarcoma)9 and MET (mesenchymal-epithelial transition)10 mutations. Some of these genetic mutations respond well to approved therapies called tyrosine kinase inhibitors (TKIs).11
Tumours can change over the course of therapy. Initial treatment might stop the growth and spread of a tumour for a period of time, but eventually the cancer may become less responsive to the treatment and may start to grow and spread again (known as progression). With EGFR and ALK mutations, this usually happens when tumours gain another mutation that may make the TKI medicine less effective.2,4,13,14,15 If it is established that a tumour is growing or spreading, further tests are usually needed to determine its molecular basis and underlying genetic changes in order to determine the best treatment option.16
AstraZeneca is committed to understanding the genetic drivers of cancer and resistance that cause cancer cells to grow through additional mutations, with the objective of extending progression-free survival. By harnessing the power of science to understand and target resistance mutations, AstraZeneca aims to redefine cancer treatment and one day eliminate cancer as a cause of death.
1 Cancer.Net; American Society of Clinical Oncology. How cancer starts. http://www.cancer.net/navigating-cancer-care/cancer-basics/genetics/genetics-cancer. Accessed April 2016
2 My Cancer Genome; Vanderbilt-Ingram Cancer Center. Lung Cancer. http://www.mycancergenome.org/content/disease/lung-cancer/egfr/. Accessed April 2016
3 American Cancer Society website. Cancer glossary. http://cancer.org/cancer/cancerglossary/index. Accessed April 2016
5 Cancer Research UK. Lung cancer tests. Available at: http://www.cancerresearchuk.org/about-cancer/type/lung-cancer/diagnosis/lung-cancer-tests. Accessed April 2016
7 U.S. National Institutes of Health. Genetics Home Reference. EGFR. Available at: https://ghr.nlm.nih.gov/gene/EGFR. Accessed April 2016
8 U.S. National Institutes of Health. Genetics Home Reference. ALK. Available at: https://ghr.nlm.nih.gov/gene/ALK. Accessed April 2016
9 U.S. National Institutes of Health. Genetics Home Reference. KRAS. Available at: https://ghr.nlm.nih.gov/gene/KRAS. Accessed April 2016
11 Langer CJ, et al. Epidermal Growth Factor Receptor Inhibition in Mutation-Positive Non-Small-Cell Lung Cancer: Is Afatinib Better or Simply Newer? Journal of Clinical Oncology. 2013;31(27);3303-3305
12 Cancer Research UK. Cancer growth blockers. Available at: http://www.cancerresearchuk.org/about-cancer/cancers-in-general/treatment/biological/types/cancer-growth-blockers. Accessed April 2016
ATLAS ID: 965601.011
Date of next review: March 2017