Kevin worked for 10 years at a uranium mine, excavating uranium for a nearby nuclear power plant. Now, 25 years later, he has small cell lung cancer

Question

Kevin is anorexic and has lost a considerable amount of weight. His muscles are wasting, and he is weak. He tries to move around the house throughout the day but tires easily. It has been difficult for him to access care, and the treatment for his cancer is just starting.

With the ongoing exposure to the ionizing radiation, DNA damage occurred. What are the three stages of carcinogenesis that occurred after his exposure to radiation?

Kevin is normally a fit and active man, and his wife often commented on how much food he used to eat after a day at the mine. Why would there be muscle wasting and weight loss now? Explain your answer using your knowledge of the metabolic changes seen with cancer.

In some cancer patients, muscle weakness may result from the production of onconeural antigens. Describe the effects of these antigens. In what form would this process likely take in Kevin's situation?

Answer 1

The three stages of carcinogenesis are as follows:
Initiation: this describes the exposure to a carcinogen. The exposure results in irreversible damage to the genome of an otherwise healthy cell. Such an exposure may be a one-time event, or it may occur in divided doses over a period of time.
Promotion: promotion may start soon after initiation or be delayed in a latent period. Promotion involves unregulated cell growth promoted by a variety of chemicals and growth factors.
Progression: this stage defines the malignant changes that occur in cells. These changes provide cancerous cells with the characteristic properties of invasiveness, metastatic competence, autonomous growth ability, and greater karyotype instability.

Fat and muscle wasting are a result of cancer anorexia-cachexia. The syndrome involves hypermetabolism and the altered processing of nutrients. Tumors consume glucose and produce lactate. Hypermetabolism occurs when, in an inefficient process, the liver uses the lactate for gluconeogenesis. The uncoupling of the oxidative phosphorylation process at the cellular level yields heat energy, contributing to poor energy utilization and hypermetabolism. Finally, instead of sparing amino acids when generating energy, muscle mass is depleted together with fat stores. Muscle wasting, weakness, and weight loss are the result.

Lambert-Eaton syndrome is a paraneoplastic neurologic disorder seen in some patients with small cell lung cancer. The cancer cells produce onconeural antigens that trigger an immune reaction. If antibodies and primed lymphocytes are able to cross the blood-brain barrier, they recognize the neurons associated with the antigen and mount an immune response against the cells.