Signs and symptoms
The majority of patients who are diagnosed with lung cancer usually present with locally advanced or metastatic disease. Only about one third of patients have stage I disease when diagnosed. The symptoms that the patient exhibits usually reflect the extent of the cancers spread. Lung cancers that are discovered early may cause symptoms localized to the respiratory system. However, lung cancer that is advanced will cause patients to experience additional signs and symptoms secondary to the cancer spreading to other organ systems. In order of highest frequency, the most common signs of lung cancer include:
cough that does not go away or gets worse
weight loss
dyspnea (shortness of breath or difficulty breathing)
chest pain, which may be aggravated by deep breathing, coughing, or laughing
hemoptysis (coughing up blood or rust-colored phlegm)
bone pain
clubbing
fever
generally feeling tired or weak
superior vena cava obstruction- facial, neck, upper torso swelling. This is caused by compression of vasculature by the lung tumor that restricts blood return from the upper body. dysphagia (trouble swallowing or the sensation that something is caught in the throat) and hoarseness
new onset of wheezing without history of asthmaClinicians should have a high level of suspicion for lung cancer, especially in patients with a smoking history. Patients with recurring or unresolving lung infections (e.g. bronchitis and pneumonia) that are unresponsive to antibiotics should also be further evaluated for lung cancer. In nonsmokers, women and East Asians are more likely to present with symptoms of an underlying lung cancer at younger ages.
Mechanism
Pathogenesis
Large scale studies such as The Cancer Genome Atlas (TCGA) have systematically characterized recurrent somatic alterations likely driving lung adenocarcinoma initiation and development. Gene mutations and copy number alterations
Since smoking is a strong mutagenic factor, lung adenocarcinoma is one of the tumor types with the highest number of mutations. Common somatic mutations in lung adenocarcinoma affect many oncogenes and tumor suppressor genes, including TP53 (mutated in 46% of cases), EGFR (27%), KRAS (32%), KEAP1, STK11 and NF1. EGFR and KRAS mutations tend to appear in a mutually exclusive fashion. KRAS mutations are associated with smoking habits, whereas EGFR mutations occur more frequently in females, people of Asian ethnicity and never-smokers.Copy number amplifications in oncogenes such as TERT, MDM2, EGFR, MET, and MYC have been reported, as well as deletions of tumor suppressor genes such as CDKN2A.Frequent alterations occur in genes belonging to the receptor tyrosine kinase pathway, of which EGFR is the most prominent example. This pathway is involved in cell proliferation and survival and it is often deregulated in cancer. As a consequence, targeted therapies have been developed to inhibit mutant pathway components. Chromosomal rearrangements
Three membrane associated tyrosine kinase receptors are recurrently involved in fusions or rearrangements in adenocarcinomas: ALK, ROS1, and RET, and more than eighty other translocations have also been reported in adenocarcinomas of the lung.In ALK rearrangements, the most common partner gene is EML4. EML4-ALK fusions tend to occur in tumors that do not carry EGFR or KRAS mutations and have also a lower frequency of TP53 mutations.