Section 9

A gene whose inactivation leads to tumor development Tumor suppressor genes are lost or inactivated in cancer cells.

Identified through studies of retinoblastoma, a rare childhood eye tumor Inherited mutations lead to susceptibility, but additional mutations are required for tumor development.

• Inheritance of a mutant copy of Rb • A second somatic mutation leading to loss of the normal Rb allele This explains why only a small fraction of cells give rise to tumors.

TRUE Non-inherited cases are rare due to the requirement of two mutations.

Most common target of mutations in human cancers Mutations of p53 play a role in about 50% of all cancers.

The formation of new blood vessels It is a critical process in tumor growth and metastasis.

• Benign tumors: confined to original location • Malignant tumors: invade surrounding tissue and metastasize Only malignant tumors are referred to as cancers.

Spread of cancer cells through the blood or lymphatic system to other organ sites It is a key factor that makes cancer dangerous.

Chemotherapeutic antibodies that bind immune checkpoint receptors or their ligands They enable T cell-mediated attack and removal of cancer cells.

Stimulation of cell proliferation by growth factor production from the responsive cell Many cancer cells produce their own growth factors.

Couple growth factor receptors to activation of Raf, leading to ERK activation Mutations in Ras lead to constitutive activity and abnormal cell proliferation.

Disrupt normal cell cycle regulation by inactivating tumor suppressor proteins This can lead to uncontrolled cell proliferation.

• Benign tumors • Malignant tumors They differ in their ability to invade and metastasize.

Inactivation of a gene leading to tumor development This is a critical mechanism in cancer progression.

Mutations that lead to increased activity of a gene This can drive abnormal cell proliferation.

Visible deletions suggest loss of the Rb gene leads to tumor development This supports the role of Rb as a tumor suppressor gene.

Stimulate cell proliferation, facilitating outgrowth of proliferative cell populations They can lead to mutations during DNA replication.

Block regulatory pathways that limit the immune response against tumors ICIs promote T-cell activation and attack of malignant cells rather than targeting cancer cells directly.

Transmit intracellular signals that inhibit T-cell activation and attack This occurs even if the T-cell receptor has recognized an antigen on the same cell.

By up-regulating expression of ligands for immune checkpoint receptors This stimulates inhibitory signals that block T-cell activation.

Enable T-cell activation and attack of cancer cells They block interactions between immune checkpoint receptors and their ligands.

CTLA-4 These studies demonstrated the potential of ICIs in enabling T cells to clear tumors.

Mice retained resistance to subsequent tumor implants This indicated long-term immune protection against cancer.

Ipilimumab It was approved in 2011 following successful clinical trials.