Английская Википедия:ALK positive lung cancer
Шаблон:Infobox medical condition ALK positive lung cancer is a primary malignant lung tumor whose cells contain a characteristic abnormal configuration of DNA wherein, most frequently, the echinoderm microtubule-associated protein-like 4 (EML4) gene is fused to the anaplastic lymphoma kinase (ALK) gene. Less frequently, there will be novel translocation partners for the ALK gene, in place of EML4.[1] This abnormal gene fusion leads to the production of a protein that appears, in many cases, to promote and maintain the malignant behavior of the cancer cells.[2]
The transforming EML4-ALK fusion gene was first reported in non-small cell lung carcinoma (NSCLC) in 2007.[3]
Signs and symptoms
The signs and symptoms of this cancer include
- A cough that doesn't go away
- Chest pain that gets worse with deep breathing, coughing, or laughing
- Hoarseness
- Weight loss without trying or loss of appetite
- Coughing up blood
- Shortness of breath
- A weak or tired feeling
- Wheezing[4]
Diagnosis
Classification
Most lung carcinomas containing the ALK gene fusion are adenocarcinomas.
Some studies suggest that the papillary adenocarcinoma and the signet ring cell adenocarcinoma[5] variants are more likely to carry this fused gene than other histological variants.
The median age at diagnosis is around 50 years and the majority are female. [4][6]
Screening
Screening for ALK positive lung cancer is now a standard of care in the United States and Canada. Screening can be done with immunostaining, FISH, or next-generation sequencing (NGS).Шаблон:Citation needed
Treatment
Crizotinib is a targeted therapy (FDA approved in 2011), manufactured by Pfizer and marketed under the brand name Xalkori and Crizalk that targets the EML4/ALK fusion gene.Шаблон:Citation needed
Ceritinib is a second generation targeted therapy (FDA approved in 2014), manufactured by Novartis and sold under the brand name Zykadia that also targets the EML4 fusion gene, but as a second generation drug it has a smaller molecule that allows superior penetration of the Blood Brain Barrier (BBB) over Crizotinib and is more capable of protecting the Central Nervous System (CNS).Шаблон:Citation needed
Alectinib another second generation targeted therapy and was approved (for this) by Japan in 2014[7] and by US FDA in 2015.,[8] manufactured by Genentech and marketed under the brand name Alecensa.
Brigatinib a second generation targeted therapy (FDA approved in 2017), manufactured by Takeda and is marketed under the brand name Alunbrig.
Ensartinib is a second generation targeted therapy (trial drug X-396), manufactured by XCovery.[9]
Lorlatinib is a third generation targeted therapy (FDA approved in 2018), manufactured by Pfizer.[10]
NVL-655 is a fourth generation targeted therapy (currently in clinical trials), developed by Nuvalent.[10][11]
Although treatment with immune checkpoint inhibitors has proved effective with some types of non-small cell lung cancer, it seems to be generally ineffective with ALK positive non-small cell lung cancer.[12]
Prognosis
Treatment with crizotinib achieves 60% response rate.[13] However, crizotinib showed no improvement on overall survival compared to chemotherapy.[14] This may be due to the fact that there was a 70% crossover rate to crizotinib in patients treated initially with chemotherapy.[15] Also, patients who tested negative for EML4/ALK fusion had a response rate to crizotinib of up to 35%.[16]
According to patient advocacy group ALK Positive, a study in December 2018 found that the median survival for people with stage 4 (IV) ALK-positive lung cancer was 6.8 years with the right care.[4]
Epidemiology
EML4-ALK gene fusions occur almost exclusively in carcinomas arising in non-smokers.[17][18] About 4% of non-small-cell lung carcinomas involve an EML4-ALK tyrosine kinase fusion gene.[19] 4–6% of lung adenocarcinomas involve the fusion gene.[13]
EML4-ALK mutation rarely occurs in combination with K-RAS or EGFR mutations.
References
External links
- ↑ Шаблон:Cite journal
- ↑ Шаблон:Cite journal
- ↑ Шаблон:Cite journal
- ↑ 4,0 4,1 4,2 Шаблон:Cite web
- ↑ Шаблон:Cite journal
- ↑ Шаблон:Cite web
- ↑ Шаблон:Cite web
- ↑ New Oral Therapy To Treat ALK-Positive Lung Cancer. Dec 2015
- ↑ Шаблон:Cite web
- ↑ 10,0 10,1 Шаблон:Cite journal
- ↑ Шаблон:Cite web
- ↑ Шаблон:Cite journal
- ↑ 13,0 13,1 Шаблон:Cite journal
- ↑ Highlights of prescribing information FDA
- ↑ Шаблон:Cite journal
- ↑ Summary of safety and effectiveness data FDA
- ↑ Шаблон:Cite journal
- ↑ Шаблон:Cite journal
- ↑ Шаблон:Cite book
