Skin cancer is a malignant growth that arises when cells found on the skin experience uncontrolled growth.

Melanoma is the deadliest form of skin cancer and is caused by the uncontrolled growth of melanocytes – the cells responsible for the color of our skin, eyes, and hair. In recent years, there has been a surge in the incidence of skin cancer, causing a heavy burden on public health. However, exciting new drug targets are being identified which are potentially life-saving.

1. Immune checkpoint inhibitors

Immune checkpoint inhibitors (ICIs) are a type of cancer treatment that help the immune system fight cancer cells. They work by blocking the signaling pathways that cancer cells use to evade the immune system’s detection.

This then allows the immune cells to attack and destroy the cancer cells.

The drugs that have been developed so far, such as Ipilimumab and Nivolumab, have a good track record for treating melanoma.

In one clinical trial involving 945 melanoma patients, the combination of Ipilimumab and Nivolumab resulted in a significant and durable response rate compared with traditional chemotherapy.

2. Oncolytic viruses

Oncolytic viruses are viruses designed to target and destroy cancer cells. They infect the cancer cells and destroy them, while leaving the healthy cells unharmed.

Oncolytic viruses have been used for the treatment of several types of cancer, including melanoma, in clinical trials.

In one study, a genetically engineered herpes virus called T-VEC was found to have a profound anti-tumor effect in patients with metastatic melanoma.

T-VEC was injected directly into the tumors, leading to regression of both injected and uninjected tumors. This promising trial led to approval of T-VEC for metastatic melanoma by the Food and Drug Administration in 2015.

3. Targeted therapies

Targeted therapies are a type of cancer treatment that targets the specific features that allow cancer cells to grow and divide rapidly.

These therapies can block the signaling pathways that cancer cells use to grow and divide, or prevent new blood vessels from forming to supply nutrients to the tumor. Targeted therapies have been approved for the treatment of melanoma.

Vemurafenib is an example of a targeted therapy drug which has been used to treat melanoma patients who carry a particular genetic mutation in their tumors. This drug targets the BRAF protein, which is involved in cancer cell growth.

Clinical trials have shown that Melanoma patients treated with Vemurafenib had a significant improvement in overall survival compared with patients treated with traditional chemotherapy.

4. Combination therapies

Combination therapy is a type of cancer treatment that uses two or more drugs with different mechanisms of action to maximize the chances of destroying the cancer cells. There are several combination therapies currently in clinical trials for melanoma.

For example, there is a clinical trial testing a combination of a PD-1 inhibitor, Pembrolizumab, with a MEK inhibitor, Trametinib.

The PD-1 inhibitor helps the immune system fight cancer cells, while the MEK inhibitor blocks the signaling pathway that cancer cells use to grow and divide. Preliminary results from this clinical trial indicate that patients treated with the combination therapy had a significantly higher response rate compared with those treated with Pembrolizumab alone.

5. Adoptive T-cell therapy

Adoptive T-cell therapy involves removing T cells (immune cells) from a patient’s body and genetically modifying them to recognize and attack the patient’s cancer cells. The modified T cells are then injected back into the patient’s body.

This type of therapy is still in the trial phase for melanoma, but promising results have been reported.

In one study, T cells were genetically modified to express a chimeric antigen receptor (CAR) that recognized a protein found on the surface of melanoma cells.

These modified T cells were then infused into melanoma patients who had failed conventional treatments. The results showed that CAR T cells induced a significant anti-tumor effect, and three out of four patients remained tumor-free at the time of publication. Although this is a small study, it offers hope for future wider adoption of this technology.

6. Proteasome inhibitors

The proteasome is a cellular mechanism that breaks down proteins that are no longer needed by cells.

Cancer cells use this mechanism to evade the immune system, as the breakdown products are used to create peptides that are displayed on the cell surface, allowing the cancer cell to evade detection. Proteasome inhibitors have been developed, such as Bortezomib, which block the breakdown of proteins and destroy cancer cells.

While Bortezomib is FDA-approved for the treatment of certain types of blood cancers, another proteasome inhibitor, Carfilzomib, is currently in clinical trials for the treatment of melanoma.

Carfilzomib has been shown to block the growth of melanoma cells in the lab, and early clinical trials show promise for future treatments.

7. PARP inhibitors

PARP inhibitors were originally developed to treat cancer in patients with mutations in the BRCA1 or BRCA2 genes. PARP inhibitors block an enzyme involved in DNA repair, causing cancer cells to die.

These drugs work best in tumors with a defect in the DNA repair process, such as those with a BRCA mutation.

However, recent studies have shown that PARP inhibitors can also be used as single agents to treat other types of cancer, such as melanoma.

Preliminary results from one clinical trial showed that patients treated with a PARP inhibitor, Talazoparib, had a longer progression-free survival compared to patients treated with traditional chemotherapy.

8. Anti-CD47 antibodies

CD47 is a “don’t eat me” signal on the surface of cancer cells that tells macrophages, a type of immune cell, to leave the cancer cells alone.

Anti-CD47 antibodies are a type of immunotherapy drug that block the CD47 signal, allowing macrophages to attack and destroy the cancer cells.

Anti-CD47 antibodies have shown promise in preclinical studies for the treatment of melanoma.

In one study, a macrophage-activating antibody called Hu5F9-G4 was combined with a PD-1 inhibitor, leading to a significant reduction in the size of tumors in melanoma mice models. Human clinical trials have been planned.

9. Anti-IDO inhibitors

Indoleamine 2,3-dioxygenase (IDO) is an enzyme produced by some tumors that suppresses the immune system, allowing cancer cells to escape detection by the immune system.

IDO inhibitors block the activity of the IDO enzyme and have been shown to activate the immune system and enhance anti-tumor immunity.

The IDO inhibitor Epacadostat has shown promise in early clinical trials for the treatment of melanoma.

In one clinical trial, Epacadostat was given in combination with a PD-1 inhibitor, which resulted in a higher disease control rate compared to those treated with a PD-1 inhibitor. This study has encouraged further trials with the drug combination.

10. Oncogene targeted therapies

Oncogenes are genes that, when mutated, can cause cancer. Targeted therapies that block the oncogenes and their products have been developed in melanoma.

Selumetinib is a drug that targets the MEK1/MEK2 gene, which plays a role in cell growth and survival. In melanoma patients, this gene is often activated by mutation, leading to uncontrollable growth of cancer cells.

In clinical trials, patients treated with Selumetinib showed a significant reduction in tumor size, and some showed a complete response of the tumors. The Selumetinib has been approved for the treatment of metastatic melanoma.

In conclusion, there are many innovative drugs under clinical evaluation that offer new hope for the treatment of melanoma.

Immune checkpoint inhibitors, targeted therapies, oncolytic viruses, combination therapies, adoptive T-cell therapies, proteasome inhibitors, PARP inhibitors, anti-CD47 antibodies, anti-IDO inhibitors, and oncogene targeted therapies are all showing promise in clinical trials. These new therapies offer much-needed hope to the many people who suffer from skin cancer.