Therapies in Development

Investigational Systemic Therapies

A number of clinical trials are ongoing with established or investigational drugs for squamous cell skin cancer. Immunotherapy agents, alone or in combination, are being studied as neoadjuvant therapy (given before surgery to shrink the tumor before surgery and to prevent recurrence after surgery) and as adjuvant therapy (therapy given after the primary treatment to prevent the cancer from coming back). Multiple investigational medications are also being studied in combination with radiation therapy to see if they work well together in squamous cell skin cancer. Drugs that are directed to specific key cellular pathways in cancer cells (targeted therapies) as well as more traditional chemotherapy drugs, which work primarily by destroying actively dividing cells such as cancer cells, are also being studied. These types of drugs may have a special role for patients who have received organ transplants because immunotherapy is riskier for this group of people.

Investigational Intratumoral Therapies

Intratumoral therapies are drugs that are delivered (injected) right into the tumor. Oncolytic viral therapies are a type of  immunotherapy that is often given intratumorally. They can be made from a modified virus to selectively target the cancer cells at the site of the injection. The injected virus reproduces within the tumor cells, which causes the affected tumor cells to lyse (break up). The therapy also delivers signals to activate an immune response at the site of the tumor, causing the immune system to come to the site and destroy additional tumor cells. A few oncolytic immunotherapies—RP1, talimogene laherparepvec, and MEM-288—are being investigated alone or in combination with systemic immunotherapies for patients with squamous cell skin cancer. These combination approaches are being tested to determine if they work better together than either type of therapy alone. For more on intratumoral therapies being studied in squamous cell skin cancer, please see

Squamous cell skin cancer happens frequently to patients who have received organ transplants, the frail elderly, and individuals with weakened immune systems. In particular, organ transplant recipients have a 65-fold to 250-fold increased risk for developing squamous cell skin cancer compared with the general population. Unfortunately, for transplant patients, the immune activation caused by systemic immunotherapy drugs (drugs like PD-1 inhibitors that cause body-wide immune activation) can pose a real threat to the transplanted organ, and in some cases, lead to organ rejection. A 2020 study that investigated the use of systemic immunotherapy in patients with cancer found that more than a third (37%) of patients experienced organ rejection, and 14% died as a result of such rejection (See Fisher 2020 article in RESOURCES).

As mentioned above, systemic immunotherapy drugs may be difficult to use in these patients, because when the immune system is activated throughout the whole body, it can cause rejection of the transplanted organ. Therefore, researchers are studying oncolytic immunotherapies to see if they can spark a localized immune response against the tumor while avoiding the whole-body immune activation and organ rejection that is associated with systemic immunotherapies. To learn more about a study investigating the use of the oncolytic immunotherapy RP1 in the organ transplant recipients with squamous cell skin cancer, see

More on Clinical Trials in Squamous Cell Skin Cancer

Clinical trials are research studies that test how well new medical approaches work.  They have an important place in your care as researchers strive to improve current cancer treatments and search for new and better ones. Clinical trials are essential for learning about cancer and how to prevent or cure it.

Our most-effective cancer treatments would not be available without the clinical trial process. Unfortunately, many people with cancer are unaware of the option for a clinical trial or are unsure about the value of participation.

Your goal is to find the best treatment available whenever you make a treatment decision.  While there may be a good standard of care for you—care that experts believe is appropriate for your specific diagnosis and treatment history—sometimes the current standard of care is not as effective as you and your healthcare team would like. Other times, the standard of care works for a time but then stops working.  In still other instances, there is no standard of care for your situation.  At these times, participation in a clinical trial may be the best option for you.

The best time to search for clinical trials is every time you are faced with a treatment decision.  

*Throughout these treatment sections, we make references to recommended treatment strategies. We consulted the American Academy of Dermatology (AAD) and the National Comprehensive Cancer Network (NCCN) guidelines on these topics. These professional groups are the foremost authorities on skin cancer management. To consult these guidelines, please see RESOURCES.

Mohs surgery image courtesy of Terese Winslow.