Locally Advanced Basal Cell Carcinoma (laBCC) is a type of skin cancer that typically arises from the basal cells of the skin’s epidermis. It is the most common form of non-melanoma skin cancer, accounting for about 80% of all skin cancer cases.

laBCC is characterized by the presence of a tumor that has invaded surrounding tissues, including muscle, cartilage, and bone, but has not spread to distant organs or lymph nodes.

Treatment Options for laBCC

The treatment of laBCC depends on the extent and location of the tumor, as well as the individual patient’s overall health.

The primary goal of treatment is the complete removal of the tumor while preserving normal tissue function and minimizing cosmetic deformity.

Surgery as a Primary Treatment

Surgery is often the primary treatment for laBCC. Several surgical approaches may be used, including:.

Excision: The tumor is surgically cut out, along with a margin of healthy skin.
Mohs surgery: The tumor is removed layer by layer, with each layer examined under a microscope until no cancer cells are seen.
Electrodesiccation and curettage: The tumor is scraped away with a curette and the base is then cauterized.

Radiation Therapy

Radiation therapy involves the use of high-energy X-rays or other types of radiation to kill cancer cells.

It is often used as an alternative treatment for patients who are not suitable candidates for surgery due to the size or location of the tumor, or for those who wish to preserve their cosmetic appearance.

Targeted Therapies for laBCC

Targeted therapies for laBCC are a relatively new approach that aims to specifically target the molecular abnormalities present in cancer cells while sparing normal cells.

Hedgehog Pathway Inhibitors

One of the key molecular abnormalities in laBCC is the dysregulation of the Hedgehog signaling pathway. This pathway plays a crucial role in normal embryonic development and tissue regeneration but is usually turned off in adulthood.

In laBCC, mutations in components of the Hedgehog pathway result in its constant activation, leading to uncontrolled cell growth and the formation of tumors.

Hedgehog pathway inhibitors, such as vismodegib and sonidegib, have been developed to selectively target and inhibit the activity of the Hedgehog pathway.

These drugs are taken orally and work by binding to a protein known as smoothened, which is a key component of the Hedgehog pathway, thereby preventing the pathway from becoming activated and halting tumor growth.

Immunotherapy

Immunotherapy is a treatment approach that harnesses the body’s immune system to fight cancer.

It involves the use of drugs that stimulate the immune system or target specific immune checkpoints to enhance the body’s ability to recognize and destroy cancer cells.

Immune checkpoint inhibitors, such as pembrolizumab and nivolumab, have shown promise in the treatment of advanced skin cancers, including laBCC. These drugs work by blocking proteins on immune cells that prevent them from attacking cancer cells.

By blocking these immune checkpoints, immune cells are unleashed to recognize and destroy cancer cells effectively.

Combination Therapy

Some studies have investigated the potential benefits of combining targeted therapies with immunotherapy in the treatment of laBCC.

The rationale behind combination therapy is to exploit different mechanisms of action to maximize treatment efficacy and overcome potential resistance mechanisms.

Potential Side Effects

Like any cancer treatment, targeted therapies for laBCC can have side effects. The specific side effects depend on the type of treatment and individual patient factors. Common side effects may include fatigue, nausea, muscle cramps, and hair loss.

However, side effects are typically manageable and reversible upon completion of treatment.

Conclusion

Targeted therapies have revolutionized the treatment landscape for locally advanced basal cell carcinoma. Hedgehog pathway inhibitors and immunotherapy have shown significant efficacy in controlling the disease and improving patient outcomes.

Further research and clinical trials are needed to optimize the use of targeted therapies and explore potential combination strategies. Overall, these advancements provide hope for patients with locally advanced basal cell carcinoma, offering effective and well-tolerated treatment options.