cancer pom questions Flashcards
im fucked
Describe the microscopic appearance of dysplastic cells.
dont forget there is a large deletion of gene CDKN2a
“Screwed up lol” -> appearance of variability between cells, reduced cellular differentiation and maturation. It will look more stem cell-like. Specifically, Pleomorphism, hyperchromatic nuclei and increase in cytoplasm to nucleus ratio.
What possible hallmarks of cancer may be present in this scenario?
“Sustaining proliferative signalling” and “evading growth suppression” because of dysplasia and cells overgrowing. The fact that the tumour has grown probably “resisting cell death” and “avoid immune destruction” as well
Describe the process the cancerous cells would have had to undergo to metastasise to distant sites.
First the cancer would need to get rid of cell-cell adhesion to separate from the primary tumour. Next they need to get through the basement membrane using metallomatrix proteases. These will degrade the membrane and help the cells have access to the blood vessels. Some of these blood vessels can be pre-existing and others formed through angiogenesis. Once in the bloodstream, cells will use specific cell signals to migrate to specific regions. For example lung cancers often, but not always, metastasize to the liver and adrenal glands. This is due to specific adhesion molecules needed to attach. These adhesion molecules differ in proteins such as E-cadherins allowing the cell to integrate into distant tissues. Now in distant sites, the patient can either have the cells sit there waiting for other signals or can start growing immediately.
Describe the role of nutrition in cancer
a) This patient’s dysphagia means he can’t swallow and therefore can’t obtain food orally
Management in short term before the tumour is resolved: alternative feeding (e.g. nasogastric/gastrostomy/jejunostomy/TPN)
If needed long-term, then gastrostomy or jejunostomy would be better in terms of patient comfort
Outline the role of genetics and how this can lead to the development of cancer
Genetic predisposition in cancer often plays a role when it comes to tumour-suppressor gene related cancers. The “two-hit theory” is applied here where both tumour suppressor genes must be dysfunctional to cause cancer. Gametic mutation in one tumour suppressor gene can lead to the “first hit”, and then the “second hit” somatic mutation is acquired via time and lifestyle factors. If an individual were not genetically predisposed, both “hits” would have to come from random somatic mutations. This is a large reason why early-onset cancers <50yrs are a clear red-flag indicating a genetic predisposition as most sporadic cancers need a long time to acquire both somatic mutation “hits”.
Describe the mechanism, initiators and promoters of lung cancer.
The nACHRs act as the promoter by causing addiction (prolonged exposure to carcinogens and dependance), damages the lung epithelial cells and promotes cancer formation, and causes angiogenesis, which promotes the cancer in the lung to survive and metastasis to distant sites. It causes DNA adducts and initiates guanine to transform into either thymine or adenine.
The initiator of the HNSCC would be mutations brought about by carcinogens in cigarette smoke such as NNK and PAH. These carcinogens cause direct mutations (G → T and G → A transitions) and forming DNA adducts in the epithelial cells of the lung.
Cigarette smoke plays both initiating and promoting roles in the progression of lung cancer. In terms of promoting, chemicals in cigarette smoke such as NNK and PAH cause direct mutations of the DNA, promoting G→T to G→A transitions. If these sporadic genetic changes occur in tumour suppressor and proto-oncogenes this can promote cancer formation. Further, these chemicals also act as promoters for lung cancer by establishing a favourable environment for tumour growth via many complex mechanisms e.g. promoting angiogenesis in endothelial cells, inducing addiction in the brain and promoting endothelial and tumour cells to grow, proliferate and invade.
How should this patient’s weight be managed in the short term to prevent further weight loss?
His laryngeal mass is likely causing obstructive dysphagia and impairing his ability to ingest an adequate food intake, leading to him falling into a protein and calorie deficit. To prevent further weight loss before the tumour itself is resolved, alternative feeding methods such as gastrostomy should be considered (or potentially intravenous feeding).
We could also make sure nutrient dense liquids are given, which are easily swallowed to make sure that muscle wasting is minimised
What are the roles of promoters and initiators in the development of this patient’s cancer?
Initiators will cause a direct mutation in the DNA sequence, while promoters create a favourable environment for mutations to occur. Certain chemicals in tobacco such as NNK and PAH play both roles.
Describe how cetuximab could be used to treat this cancer and how it elicits its effect.
Cetuximab is a monoclonal antibody that binds the external part of EGFR to prevent ligand binding, inhibiting them from driving the uncontrolled cell proliferation.
Give a reason why cetuximab may be rendered ineffective in this case
The EFGR usually enhances cell proliferation and survival by turning on intermediate molecules such as KRAS. Cetuximab acts on the EFGR to turn off/reduce cell proliferation and survival. In a case where KRAS is mutated, it will remain constantly on despite the upstream signals it receives from EFGR, so cell proliferation and survival will always remain on. Therefore, cetuximab won’t work because it controls KRAS via the EFGR. Mutant KRAS acts in a dominant allele fashion and so only requires one mutant allele to prevent cetuximab function.
What mechanisms could this tumour have used to evade your patient’s immune system?
Immune checkpoints, even if the cancer cells are expressing a neo-antigen from an accumulation of mutations in the DNA, immune checkpoints may stop T cells from reacting. The cancer cells may have also cloaked themselves from phagocytes while circulating in lymphatic vessels.
