What is Basal Cell Carcinoma?
Basal cell carcinoma (BCC) is the most common form of cancer and comprises approximately 80 percent of non-melanoma skin cancers. More than 1 million people receive treatment for BCC each year in the United Sates.
Risk Factors for Basal Cell Carcinoma
The following factors increase an individual’s risk for developing basal cell carcinoma:
- Having grey, green, or blue eyes
- Having freckled or light skin
- Having red or blonde hair
- Having multiple moles
- Overexposure to radiation such as X-rays
- A family history of skin cancer
- Daily sun exposure for long periods of time
- A number of serious sunburns in early life
Symptoms of Basal Cell Carcinoma
Basal cell carcinoma may develop in various ways. In some cases the skin may appear flat or slightly raised; in others BCC may appear as a skin growth or bump that could look light pink or white, "waxy" or "pearly," or brown or flesh tone.
Basal Cell Carcinoma Treatments
The vast majority are of basal cell carcinoma cases are treated with localized procedures such as the following:
- Excisional or Mohs surgery
- Radiation therapy
- Photodynamic (light) therapy
- Topical therapies
- Cryosurgery (killing cancer cells by freezing them)
- Electrodesiccation (using electricity to scrape cancer cells away)
On rare occasions the BCC can continue to grow despite surgery and radiation therapy. Even rarer, BCCs can metastasize distantly in the body to other sites such as the lungs.
Advanced Disease and Treatment
The majority of BCCs have developed activating mutations in a signaling pathway called the Hedgehog (Hh) signaling pathway. Abnormal activation of this pathway leads to the proliferation of basal cells contributing to the development of BCCs. The most common mutation in the Hh pathway is the loss of activity of a protein called Patched Homologue 1 (PTCH1). PTCH1 normally binds to another protein called Smoothened (SMO) and blocks the activity of SMO. Active SMO leads to activation of other proteins called Gli proteins and subsequently to the proliferation of cells.
As such, the loss of PTCH1 activity prevents PTCH1 from blocking the activity of SMO. Therefore SMO is active and activates Gli proteins and leads to the proliferation of basal cells.
As an alternative to the loss of PTHC1 activity, some BCCs develop inactivating mutations directly in SMO. As such the activity of SMO is decreased leading to less Gli activity and less proliferation of basal cells.
A treatment called vismodegib (Erivedge) which blocks the activity of SMO was approved by the FDA for the treatment of BCCs that metastasized distantly or that have progressed locally and are no longer amenable to surgical or radiation based interventions.
Vismodegib is taken orally at a dose of 150 milligrams once every day. In the study that led to FDA approval 30 percent of patients with metastatic BCC and 43 percent of patients with locally advanced BCC developed a response. The median duration of response was 7.6 months. Side effects seen in more that 30 percent of patients included but not limited to muscle spasms or cramps, taste alteration, loss of weight, and fatigue.
Given the rarity of distantly metastatic or locally advanced BCC, it is important to have this condition managed by an experienced, multidisciplinary team.