302 Cancer biology: metastasis and prognosis

Question 1

What are some different types of colorectal cancer?

Answer 1

-Colon cancer
-Rectal cancer
-Oligometastatic disease
-Widespread metastatic disease

Question 2

What is an adenocarcinoma?

Answer 2

Malignant transformation of glandular epithelium

Question 3

What is Familial Adenomatosis Polyposis Coli?

Answer 3

inherited loss of APC, inevitable second hit > multiple polyps (hundreds) > inevitable subsequent driver mutations > cancer

Question 4

What is Hereditary Non-Polyposis Colon Cancer (HNPCC)?

Answer 4

An inherited mutation in one of the genes involved with mismatch repair > multiple point mutations > increased risk of CRC, endometrial, small bowel and pancreatic cancers

Question 5

What cellular dysfunctions are commonly present in colorectal cancer?

Answer 5

RAS/RAF/MEK/ERK or PI3 Kinase signalling

Activating mutations in K-RAS occur in approx 40% CRC, especially in polyp > cancer progression and left sided / rectal cancers

Question 6

How is colorectal cancer treated with different mutations?

Answer 6

Chemoinnunotherapy

Cetuximab – anti EGFR antibody (but ineffective if KRAS mutation)

Encorafinib – blocks mutant BRAF – in combination with Cetuximab appears to control disease

Immune checkpoint inhibitors (that unmask cancer cells for immune clearance) now licensed in MMR deficient CRC (but ineffective in MMR proficient tumours)