Lung Cancer Vignette Flashcards
What are the incidence, death rates, and 5 year survival of lung cancer in the US in 2012?
226,000 new cases; 160,000 deaths. More deaths per 1000 than next four cancers combined (160 lung vs. 158 others). 5 year survival = 12% in 1977 and 16% in 2007.
What are the typical stages of lung cancer at the time of diagnosis?
15% stage I or II, non-metastatic 50% stage IIIa or IIIb, local metastasis 35% stage IV, distant metastasis
Which stage of lung cancer has the poorest prognosis?
Stage IIIb
What are the two general types of biomarkers?
Prognostic biomarkers - give information of the prognosis of the disease independent of treatment. Predicitive biomarkers - give information indicating the likely outcomes of specific treatments.
What are the two general types of lung cancers?
Small Cell Lung Cancer (15% of cases) and Non Small Cell Lung Cancer (85% of cases). NSCLC is subdivided into Squamous Carcinoma, Adenocarcinoma, and Large Cell & Others but these classifications do not have clinical implications.
What are targeted therapies?
Targeted therapies are agents that work against specific biologic pathways. More than 50% of Non-Small Cell Lung Cancers have targeted therapies.
What is EGFR?
EGFR is a member of the HER family of Tyrosine receptor kinases. They have a cystein rich domain on the extracellular surface and bind many types of ligands. Mutations in the EGFR gene can cause constitutive activation of EGFR receptors.
How can dysregulation of EGFR occur?
Through overexpression of the ligand, receptor over expression, or mutations affecting the ATP binding site in the Tyrosine Kinase Domain.
What pathways does the EGFR receptor activate?
The PI3 and GRB/SOS -> Ras/Raf pathways.
What are the two types of drugs that inhibit EGFR and where do they work?
There are EGFR-TKI (Tyrosine Kinase Inhibitors) that act on the intracelluler TKD, and Antibodies that act on the extracellular receptor domain.
What percentage of patients in the US have EGFR mutations? In Asia?
10% of lung cancer patients have these mutations in the US. In Asian populations, the rate is 50%.
What is a major Tyrosine Kinase Inhibitor (EGFR-TKI) used to treat EGFR (+) patients?
Gefitinib (Iressa)
What are the benefits of using next generation sequencing in cancer diagnosis?
You can detect mutations, DNA copy number mutations, translocations/fusions, and RNA sequencing can show gene-expression and alternative splicing. It can detect known and unknown mutations.
What causes the Anaplastic Lymphoma Kinase (ALK) mutation that results in lung cancer, how is it detected, and what are the survival times with treatment?
The ALK gene is located on chromosome 2, very close to the EML4 gene. Translocations cause a fusion gene product EML4-ALK. This can be detected via FISH, ALK-Protein Expression, or PCR. ALK inhibitors produce upto a 10 month progression free survival in patients previously on chemotherapy, but only in the 3% of patients with the ALK rearrangement.
What is the breakdown of subtypes in NSCLC and how does this lead to personallized treatment?
There are far more targets now known in NSCLC. Each of these mutations may lead to targeted therapies, improving survival for those who have specific mutations. Over 50% of NSCLC cases now have targeted therapies.
