Targeted Therapy for Cancer

Traditional cancer treatments like chemotherapy and radiation work by killing all rapidly dividing cells. Because some of our normal cells divide rapidly too, these treatments kill many normal cells in addition to killing cancer cells. This results in side effects like nausea, vomiting, diarrhea, hair loss, and low blood counts.

Targeted therapies work by targeting the parts of cancer cells that are different from normal cells: a mutated receptor or mutated signaling protein. Ideally, targeted therapies block the growth signal in cancer cells much more than in normal cells, making them more effective therapies with fewer side effects. However, most current targeted therapies do cause significant side effects.

The cell receives a growth signal
receptorligandsignaling pathwayGROWTH

In both normal and cancer cells, a ligand binds a receptor which transmits growth signals to the cell via a signaling pathway. Mutations in some of these proteins can cause this growth signal to be constantly “on” and lead to uncontrolled cell growth.

  

Proteins called receptors live on the surface of cells. When a protein called a ligand binds to the receptor outside the cell, the receptor transmits the signal to the inside of the cell. This results in normal cell division and growth. Mutations in these receptors can cause this growth signal to be constantly “on” and lead to uncontrolled cell growth. Sometimes mutations occur in one of the signaling proteins inside the cell also causing constantly “on” growth. In either case, uncontrolled cell growth may result in the development of cancer.

Targeted therapies can block transmission of the growth signal at multiple points, as shown in the figures below:

Blocking the receptor outside the cell
Targeted therapy can bind to the ligand outside the cell, prevent the ligand from binding its receptor, and thus prevent transmission of the growth signal to the cell. Rilotumumab (being tested for lung cancer) works in this way. Targeted therapyNO GROWTH
Targeted therapy can bind directly to the receptor, preventing the normal ligand from binding to the receptor. Cetuximab (approved for colorectal cancer and others) and trastuzumab (approved for HER2-overexpressing breast and stomach cancer) work in this way. Targeted therapyNO GROWTH
Targeted therapy can bind to the ligand outside the cell, prevent the ligand from binding its receptor, and thus prevent transmission of the growth signal to the cell. Rilotumumab (being tested for lung cancer) works in this way.
Targeted therapy can bind directly to the receptor, preventing the normal ligand from binding to the receptor. Cetuximab (approved for colorectal cancer and others) and trastuzumab (approved for HER2-overexpressing breast and stomach cancer) work in this way.

  

Blocking the receptor inside the cell
Inside the cell, targeted therapies can bind to the receptor and prevent transmission of the growth signal from the receptor to the signaling pathway. Erlotinib (approved for lung cancer with EGFR mutations) and lapatinib (approved for HER2-positive breast cancer) work in this way. Targeted therapyNO GROWTH
Targeted therapies can also block one of the proteins in the signaling pathway, downstream from the receptor. Trametinib (approved for melanoma with BRAF mutations) and everolimus (approved for kidney cancer and others) work in this way. Targeted therapyNO GROWTH
Inside the cell, targeted therapies can bind to the receptor and prevent transmission of the growth signal from the receptor to the signaling pathway. Erlotinib (approved for lung cancer with EGFR mutations) and lapatinib (approved for HER2-positive breast cancer) work in this way.
Targeted therapies can also block one of the proteins in the signaling pathway, downstream from the receptor. Trametinib (approved for melanoma with BRAF mutations) and everolimus (approved for kidney cancer and others) work in this way.

Learn more about specific targeted therapies