Targets for Cancer Therapy Lecture Flashcards

Vocabulary-style flashcards covering cancer therapy targets including biologics, tyrosine kinase inhibitors, checkpoint inhibitors, and PARP inhibitors.

Biologics

Agents that target and prevent proliferation, inhibit angiogenesis, help deliver radio/chemotherapy, and act within the immune system to stimulate or prevent inhibition of the immune response to cancer cells.

Cetuximab

A chimeric monoclonal antibody ($Mab$) that binds to and inhibits $EGFR/HER1$.

Trastuzumab

A humanised monoclonal antibody ($Mab$) that targets $HER2$ and inhibits tumour cell proliferation by preventing dimerization and inducing receptor downregulation via endocytosis and proteolysis.

Bevacizumab

An agent that binds to vascular endothelial growth factor ($VEGF-a$), preventing it from binding to its receptor to inhibit angiogenesis.

ADCC (Antibody-Dependent Cellular Cytotoxicity)

A cytotoxic immune response facilitated by the binding of antibodies like Trastuzumab, which activates natural killer cells and macrophages.

Gefitinib

A 1st generation $HER1$ receptor tyrosine kinase inhibitor that reversibly binds to wildtype and mutated receptors to inhibit phosphorylation.

Afatinib

A 2nd generation $HER1$ receptor tyrosine kinase inhibitor that irreversibly binds to wildtype and mutated receptors.

$$T790M$$

A resistance mutation involving a single amino acid change that leads to structural alterations in the kinase domain, preventing Gefitinib and Afatinib from binding.

Osimertinib

A 3rd generation kinase inhibitor used to overcome resistance by irreversibly binding to receptors with the $T790M$ mutation; it has reduced side effects because it does not target wildtype receptors.

Vemurafenib

A $B-RAF$ kinase inhibitor with selectivity for the ATP binding site with the $V600E$ mutation; it also acts as a $CYP1A2$ inhibitor and $CYP3A4$ inducer.

Trametinib

A reversible $MEK1$ and $MEK2$ kinase inhibitor that binds to $S218$ in the activation loop of the enzyme to prevent phosphorylation by $RAF$ and subsequent $ERK$ activation.

Palbociclib

A reversible inhibitor of $CDK4$ and $CDK6$ that prevents phosphorylation of $RB$ (retinoblastoma), causing cell cycle arrest and blocking cell cycle progression.

Rituximab and Ofatumumab

Monoclonal antibodies that bind to $CD20$ expressed on $B-cells$ to recruit macrophages, natural killer cells, and complement proteins for $B-cell$ destruction.

Blinatumomab

A human bi-specific-T-cell-engager ($BiTE$) composed of two variable regions that recognise $CD19$ (B-cell) and $CD3$ (cytotoxic T-cell) to tether them together for destruction.

$$CTLA-4$$

An inhibitory protein expressed on the surface of activated T-cells that binds to $CD80/86$ on antigen-presenting cells to downregulate T-cell function.

$PD-1$ and $PD-L1$

Checkpoint proteins where the binding of $PD-L1$ to $PD-1$ triggers T-cell apoptosis, commonly used by cancer cells to evade the immune system.

Ipilimumab

A human antibody that binds to $CTLA-4$ to prevent the downregulation of T-cell function.

Nivolumab

A human antibody that binds to $PD-1$, preventing $PD-L1$ binding and allowing T-cells to stay active to attack cancer cells.

Atezolizumab

A humanised antibody that binds directly to $PD-L1$ to inhibit its interaction with checkpoint proteins.

$PARP$ (Poly ADP Ribose Polymerase)

An enzyme involved in the repair of single strand breaks in DNA by attracting repair enzymes for base excision repair.

Olaparib and Niraparib

Small molecule $PARP$ inhibitors that inhibit single strand break repair and trap $PARP$ on DNA, leading to double strand breaks and stalling of DNA replication.

Homologous Recombination Deficiency

A condition (e.g., in $BRCA$ mutation containing tumours) where $PARP$ inhibitors are used as monotherapy because the cells cannot repair the resulting double strand breaks.