Clinical Correlation Cancer

Question 1

What do the tyrosine kinase inhibitors and monoclonal antibodies differ in terms of route of administration and half-life?

Answer 1

TKIs = short half life, taken orally

Monoclonal Abs = long halflife, given IV

Question 2

What drug is the prototypical VEGF monoclonal antibody and how does it work?

Answer 2

bevacizumab - the beverage lady

Works by binding the VEGF ligands to prevent downstream signalling and impede angiogenesis to tumors

Question 3

What tumors is bevacizumab used for?

Answer 3

Colorectal and lung cancers

Question 4

What pathways does bevacizumab inhibit by binding VEGF ligand?

Answer 4

Ras/MAPK pathway and PI3-kinase / Atk
(protein kinase B) pathway

Decreased functional vasculature to tumors

Question 5

What are the adverse effects of bevacizumab?

Answer 5

Bleeding (blood on beverage lady’s shirt)
Hypertension (increases peripheral vascular resistance)
Proteinuria (altered kidney blood flow)

Question 6

What drug is a VEGF tyrosine kinase inhibitor? What type of cancer does it primarily treat?

Answer 6

-tinibs are tyrosine kinase inhibitors (nib of pen)

Sunitinib (sun outside the building with VEGF vegetables in the field) - binds into TK active site and inhibits phosphorylation

Treats renal cell cancer (flank crab buckles on farmer)

Question 7

What other cancers does sunitinib treat and how?

Answer 7

Gastrointestinal stromal tumors -> crossreactive with platelet-derived growth factor receptor (PDGFR) and c-KIT

Question 8

What are the common toxicities of sunitinib?

Answer 8

Hypertension (like bevacizumab)
Fatigue
Hypothyroidism (mechanism unknown)

Question 9

What drug is an EGFR 1 monoclonal antibody? EGFR tyrosine kinase inhibitor?

Answer 9

EGFR 1 monoclonal antibody - cetuximab - think tusks of elephant with GiRaFeE on his saddle

EGFR tyrosine kinase inhibitor - erlotinib - think Earl of Tinib with Geoffrey on his head

Question 10

What cancers is cetuximab useful for?

Answer 10

Colorectal adenocarcinomas and head and neck squamous cell cancers

Question 11

What type of pathology must be present to effectively treat cancer with cetuximab?

Answer 11

Normal KRas/NRas biology -> if mutated, EGFR receptor will not be driving pathology, and it will not be effective

Question 12

What are the toxicities of cetuximab?

Answer 12

Rash - in almost all patients (think of red spots on the giraffe)
Hypersensitivity - think of elephant sicking serum sickness cup (chimeric antibody)

Question 13

What cancer type is erlotinib used for?

Answer 13

EGFR-mutated non-small cell lung cancers (exons 19 and 21)

Question 14

What are the toxicities of erlotinib?

Answer 14

Rash (think of the Earl’s rash)

Diarrhea (think of his soiled pants)

Question 15

What is the important EGFR2 antibody and what are its mechanisms?

Answer 15

Trastuzumab - Think of tapestry

Activity against HER2 receptor -> think of her two kids in the tyrosine kinase wheel

Also has ADCC activity - antibody-directed cell-mediated cytotoxicity

Question 16

What cancers is trastuzumab useful for?

Answer 16

Breast cancer (think of breast cancer crabs on her bobs)

Some GI cancers

Question 17

What is the unique toxicity of trastuzumab?

Answer 17

Cardiotoxicity - think of hearts hanging from her tapestry

Question 18

What drug is the prototype Antibody-drug conjugate and when is it used?

Answer 18

Trastuzumab (tapestry) with emtansine

Emtansine is a mitotic spindle inhibitor to breast cancer

Used in advanced HER2 positive breast cancer (her 2 kids)

Question 19

What drug is an anti-PD-1 monoclonal antibody and how does it work?

Answer 19

Nivolumab - binds the PD-1 receptor on T-cells so it cannot bind the PD-L1 of cancer cells which will induce apoptosis of that T cell line

Question 20

What is nivolumab used to treat?

Answer 20

Melanoma, lung cancer, and kidney cancer

Question 21

What are the toxicities of nivolumab?

Answer 21

Everything related to overactive T cells (since reactive ones cannot be easily apoptosed)

Includes:
Colitis
Pneumonitis
Hepatitis
Rash

Lung, liver, and colon inflammation