Table of Contents

I. Introduction
II. Hedgehog Pathway Inhibitors for Basal Cell Carcinoma
• Understanding the Pathogenesis of Basal Cell Carcinoma
• Hedgehog Pathway Inhibitors as Treatment
• Efficacy and Survival Rates
III. Slowing the Progression of Melanoma
• Role of Gut Microbiome in Cancer Treatment
• Immunotherapy-Microbiome Clinical Trial
• Potential Impact on Future Cancer Treatment
IV. Treatment of Melanoma Skin Cancer using Hybrid Nanofibers
• Nanotechnology in Biomedical Applications
• Targeting Tumors with Nanofibers or Nanoparticles
V. Avelumab as the Initial Approved Treatment for Merkel Cell Carcinoma
• Definition of Merkel Cell Carcinoma
• Treatment Options
• Approval of Avelumab by FDA
• Clinical Trial Data and Efficacy
VI. Drug Cemiplimab now Approved for Treatment of Advanced Squamous Cell Skin Carcinoma
• Definition of Squamous Cell Carcinoma
• Immunotherapy Drug Cemiplimab
• Approval for Advanced SCC Treatment
• Immune Checkpoint Inhibitors
VII. Conclusion

Skin cancer is one of the common forms of cancer and most of them can be treated if detected in the early stage of the disease. In the US alone, annually more skin cancers are identified than any of the other cancers and have been growing over the decades. The common types of skin cancers are basal cell carcinoma, squamous cell carcinoma and melanoma. Most of them develop as the result of exposure to ultraviolet rays including from the sun and from indoor tanning beds which damages DNA and inhibits their repair. Therefore the use of sunscreens can help lower the chances of developing squamous cell carcinoma and could also reduce the incidence of melanoma and basal-cell carcinoma. However, an increase in the rate of skin cancer incidence only indicates the need for additional preventive measures. The diagnosis for skin cancer involves an initial clinical screening followed by dermoscopic analysis, a biopsy and histopathological examination. By determining the type of skin cancer, appropriate treatment can be initiated in the early stage of the disease. Recently, a randomized controlled trial involved participants who received nicotinamide twice daily or placebo for a period of 12 months. The trial has illustrated that nicotinamide, a form of vitamin B3 can help lower the chances of developing new nonmelanoma skin cancers.  As nicotinamide is widely available, this illustrates a new opportunity for the chemoprevention of nonmelanoma skin cancer.

Hedgehog Pathway Inhibitors for Basal Cell Carcinoma

Basal cell carcinomas (BCC) are considered the most commonly developing forms of skin cancer that occurs in the skin’s basal cells lining the deepest layer of the epidermis and usually appears as red patches, open sores, pink growths or scars.  Although this form of cancer almost never spread to other parts of the body, on rare occasions it could and become life-threatening. Research has helped understand the pathogenesis of basal cell carcinoma and encouraged the development of several new generation nonsurgical interventions. Most of the basal cell cancers develop because of mutation in genes involved in the cell signaling pathway called hedgehog. As targeted therapy for basal cell skin cancers, hedgehog pathway inhibitors such as vismodegib (Erivedge) and sonidegib (odomzo) can be used for advanced or recurrent cancers. Although these drugs have shown to reduce the size of tumors among some cases, it is not yet clear if their survival rate is longer.

Slowing the Progression of Melanoma

One of the most dangerous forms of skin cancer, melanoma can develop in the pigment-producing melanocytes of the epidermis often resembling moles. A majority of them are black or brown although it could also be red, pink, purple skin-colored or white. A study shows that a greater diversity of bacteria in the gut microbiome is associated with good response to cancer treatment and longer progression-free survival. As an individual’s microbiome is associated with their response to immunotherapy, it can be used to assess their fitness for immunotherapy and to manipulate it to improve the course of treatment in the future. As the role of microbiome is involved in several functions of the body such as priming of the immune system, a first immunotherapymicrobiome clinical trial is hoped to be launched soon.

Treatment of Melanoma Skin Cancer using Hybrid Nanofibers

The current trend is the use of nanotechnologies for various biomedical applications and nanotechnology has the potential to greatly impact on the health system by making changes in the diagnosis of a disease, monitoring, regenerative medicine and drug delivery. This new technology can help with delivering and releasing drugs in a less invasive manner. However, further research is required for the development of a topical drug delivery system by microemulsion for topical application. Targeting the tumor is important with either drug-loaded nanofibers or nanoparticles which could provide greater results with melanoma therapy.

Avelumab as the Initial Approved Treatment for Merkel Cell Carcinoma

Merkel cell carcinoma is diagnosed in less than 2,000 individuals in the United States and most of them are either elderly or presenting a weakened immune system. The tumors usually develop because of a virus called Merkel cell polyomavirus which can be detected among healthy individuals but occasionally can result in cancer. Although the current treatment involving chemotherapy can shrink the growth of the tumor, it begins to grow within 6 months. Recently, Immunotherapy drug called avelumab was approved by the Food and Drug Administration (FDA) for treating some individuals with the aggressive merkel cell carcinoma. The clinical trial data shows that around 74% of the patients who had responded to the drug continued to respond lasting for more than a year. Avelumab belongs to drugs known as immune checkpoint inhibitors which ‘remove the brakes’ on the immune system, therefore, enabling the body’s immune system to effectively destroy the cancer cells.

 Drug Cemiplimab now Approved for Treatment of Advanced Squamous Cell Skin Carcinoma

Squamous cell carcinoma (SCC) is considered the second most common form of skin cancer. The lesions associated with SCC can look like warts, open sores or scaly red patches causing deformity to the surrounding skin and tissue continuing to spread throughout the body. Recently, FDA has approved the use of the immunotherapy drug called cemiplimab for individuals with the advanced form of cutaneous squamous cell carcinoma (SCC). This use of the drug is approved for individuals with metastatic or locally advanced SCC who cannot receive surgery or radiation therapy. This drug also belongs to the class of agents known as immune checkpoint inhibitors which are used to strengthen the body’s own immune response to target the tumors.

 Drugs effective against Melanoma that has spread to the brain

Clinical trials have illustrated that the combination of nivolumab and ipilimumab has stopped the growth or reduced metastatic brain tumors among more than half the participants. The drugs are also immune checkpoint inhibitors and among some of the patients, it has delivered long-lasting response and therefore could be considered as first-line therapy for those with brain metastases. According to a study in 2010, individuals with melanoma that has spread to the brain, only around 5% continue to live more than 5 years after diagnosis. However, with the recent development of new immunotherapies, the survival rates could be changing.