Targeted cancer therapies

What are targeted cancer therapies?

Targeted cancer therapies are drugs used to treat certain malignant tumours by blocking the action of particular molecular targets such as genes and proteins. They are classified as small molecules or monoclonal antibodies.

They are also called precision medicines.

How do targeted cancer therapies work?

Targeted cancer therapies interact with a target molecule to prevent tumour cells proliferating.

• The target molecule may be present in several different types of tumour. 
• The molecule may be specific to a tumour (due to mutation) or may be more abundant in a tumour than in normal cells. 
• This reduces the damage done to surrounding normal cells.
• Some drugs target fusion proteins, due to chromosomal abnormalities in the tumour.

Targeted cancer therapies are classified as:

• Hormone therapy
• Signal transduction inhibitors
• Gene expression modulators
• Apoptosis inducers
• Angiogenesis inhibitors
• Immunotherapy.

Who gets targeted cancer therapies?

Targeted therapies are currently used in dermatology for patients with advanced cancers. They are also used in clinical trials as adjuvant therapy (supplementary treatment given to people who are in remission from their cancer but are at high risk of relapse in the future). 

Satellite melanoma metastases

Scarring from multiple basal cell carcinomas

Cutaneous lymphoma

What targeted therapies are available?

Several targeted therapies are marketed in dermatology to treat advanced skin cancers, and others are in development.

Melanoma

Several products are marketed to treat unresectable metastatic melanoma.

• Vemurafenib and dabrafenib target mutant cell growth signalling protein BRAF V600E.
• Trametinib inhibits the mitogen-activated protein kinase (MAPK) signalling pathway.
• Cobimetinib is a mitogen-activated protein kinase kinase (MEK) inhibitor taken in combination with vemurafenib.
• Ipilimumab targets cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4).
• Pembrolizumab targets the programmed cell death 1 (PD-1) receptor.
• Nivolumab is a PD-1-blocking antibody.

Basal cell carcinoma

Vismodegib and sonidegib are available treatments for advanced basal cell carcinoma. They target Smoothened, a protein involved in the abnormal Hedgehog signalling pathway.

Squamous cell carcinoma

Several products are being investigated to treat advanced cutaneous squamous cell carcinoma; these include:

• Products targeting mutations in the NOTCH gene and TP53 mutations
• Immune checkpoint inhibitors (drugs that target cancer cells for elimination by the immune system). The first of these, cemiplimab, was registered by the FDA in 2018. 

Merkel cell carcinoma

• Avelumab is available to treat metastatic Merkel cell carcinoma.
• PD-1 checkpoint inhibitors are under investigation.

Cutaneous T-cell lymphoma and Kaposi sarcoma

Targeted treatments used in refractory cutaneous T-cell lymphoma and Kaposi sarcoma are based on the retinoid pathway.

• Bexarotene is a rexinoid that targets the retinoid X receptor. 
• Alitretinoin gel is used for Kaposi sarcoma.

Cutaneous B-cell lymphoma

Rituximab is used in cutaneous B-cell lymphoma. Rituximab targets the CD20 antigen found on B cells.

Dermatofibrosarcoma protuberans

Imatinib is used as a treatment in dermatofibrosarcoma protuberans. Imatinib targets BCR-ABL fusion protein. 

What are the side effects of targeted therapy?

Targeted therapies have many side effects, including adverse cutaneous reactions. In some cases, side effects are associated with excellent tumour response.

See Cutaneous adverse effects of checkpoint inhibitors and individual drug topics for more details. 

How effective are targeted therapies?

The efficacy of targeted therapies is variable. They may lose their efficacy over time, having been initially successful at reducing tumour growth and in some cases leading to complete remission.

See individual drug topics for more details.