Genetic alterations in lung cancer: Diverse forms, reasons, therapies, and further facts
Lung cancer, one of the most prevalent types of cancer worldwide, accounts for around 12-15% of all cancer diagnoses [1]. This disease is primarily caused by gene mutations, which can be due to inherited factors or exposure to carcinogens, most notably tobacco smoking, which is believed to cause around 85% of lung cancer cases [2].
Common gene mutations associated with lung cancer include TP53, EGFR, ALK, HER2, PIK3CA, FGFR3, and CDKN2A. These mutations affect treatment outcomes by influencing responsiveness to targeted therapies [3].
TP53 mutations are frequent, especially linked to exposure to air pollution, and tend to be associated with tumor progression and poorer prognosis [1]. On the other hand, EGFR mutations, more common in lung cancers, notably in non-smokers, and people of Asian descent, often respond well to EGFR tyrosine kinase inhibitors such as gefitinib and erlotinib [3][4]. ALK rearrangements also occur in subsets of lung cancer patients and are treatable with ALK inhibitors.
HER2 mutations, found in a subset of pulmonary adenocarcinomas, particularly in younger patients with smaller tumors, may provide additional targets for therapy [2][5]. PIK3CA, FGFR3, and CDKN2A mutations are also observed but less commonly and have varying implications for targeted treatments.
The presence of these mutations guides personalized medicine approaches, improving treatment outcomes by selecting therapies such as tyrosine kinase inhibitors for EGFR or ALK alterations. However, mutations like TP53 often correlate with more aggressive disease and may be linked to resistance to some therapies [1][2][4].
EGFR mutations are less common in lung squamous cell carcinoma (SCC), occurring in around 6% of lung SCC tumors [3]. In contrast, EGFR mutations occur in around 50% of all lung adenocarcinomas. Similarly, KRAS mutations are found in around 30% of all lung adenocarcinomas and 30% of lung SCCs. The PIK3CA mutation may lead to faster disease progression and is found in around 15% of lung adenocarcinomas and 6% of lung SCCs [3].
The outlook for stage 1 lung cancer is better, with around 50% of patients surviving for another 5 years if they undergo surgical treatment [6]. However, the outlook for stage 4 lung cancer is less favorable, with only 2-13% of patients surviving for another 5 years [6].
In conclusion, understanding the genetic makeup of lung cancer is crucial for effective treatment and prognosis assessment. Personalized medicine strategies, based on the identification of these genetic alterations, can lead to improved treatment outcomes and a more optimistic outlook for patients.
References: [1] National Cancer Institute. (2021). Lung Cancer: Statistics. Retrieved from https://www.cancer.gov/types/lung/statistics [2] National Cancer Institute. (2021). Lung Cancer: Treatment Options by Stage. Retrieved from https://www.cancer.gov/types/lung/hp/lung-treatment-pdq [3] National Cancer Institute. (2021). Targeted Therapies for Lung Cancer. Retrieved from https://www.cancer.gov/types/lung/patient/lung-targeted-therapy-pdq [4] American Cancer Society. (2021). What Should I Know About Targeted Therapy for Lung Cancer? Retrieved from https://www.cancer.org/cancer/lung-cancer/treatment/targeted-therapy.html [5] National Comprehensive Cancer Network. (2021). NCCN Guidelines: Non-Small Cell Lung Cancer. Retrieved from https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf [6] American Cancer Society. (2021). What's the Outlook for People with Lung Cancer? Retrieved from https://www.cancer.org/cancer/lung-cancer/detection-diagnosis-staging/survival-rates.html
- A relatively high percentage of lung cancer cases are diagnosed each year, and these cancers are often caused by gene mutations, such as TP53, EGFR, ALK, HER2, PIK3CA, FGFR3, and CDKN2A.
- Non-smokers, people of Asian descent, and individuals diagnosed with nonsmallcelllungcancer may have EGFR mutations, which can be treated effectively with certain medications like gefitinib and erlotinib.
- ALK rearrangements in a subset of lung cancer patients can also be treated using ALK inhibitors as part of personalized medicine strategies.
- The presence of gene mutations like TP53, which are frequently linked to exposure to air pollution and associated with tumor progression and poorer prognosis, may pose challenges to treatment and health-and-wellness outcomes.
