Treatment Of Melanoma With Ferroptosis Inducing Agents

Case 2017-879

UCLA researchers in the Departments of Molecular and Medical Pharmacology and Medicine have developed a novel method to treat melanoma.

BACKGROUND

Immune checkpoint blockade immunotherapy with anti-PD1 antibody is the preferred treatment for patients with metastatic melanoma that has resisted other therapies. However, there remains a subset of patients that does not respond to or relapses following this therapeutic strategy, as de-differentiation of melanoma cells is known to increase resistance to conventional immunotherapies. So far there is no therapy specifically tailored to target these immunotherapy-resistant de-differentiated melanoma cells.

INNOVATION

Researchers at UCLA have developed a method to treat melanoma that resists conventional immune checkpoint blockade immunotherapy by using ferroptosis-inducing drugs. Ferroptosis is a type of cell death resulting from accumulation of reactive oxygen species that degrade lipids in the cell membrane. De-differentiating cells, such as the immunotherapy-resistant or kinase inhibitor-resistant melanoma, are highly susceptible to ferroptosis. Combination treatment with ferroptosis-inducing agents can be a valuable, new synergistic approach for overcoming resistance to melanoma therapy.

APPLICATIONS

• Combinatorial therapy for cancer treatment
• Stratification method for skin cancer treatment
• Screening method for immunotherapy-resistant or kinase inhibitor-resistant melanomas

ADVANTAGES

• Specifically targets a subset of cancer cells that resist other forms of therapy
• Combinatorial use with conventional immunotherapy or kinase inhibitors prevents tumor escape due to de-differentiation

RELATED MATERIALS

• Titz, Bjoern, et al. "JUN dependency in distinct early and late BRAF inhibition adaptation states of melanoma." Cell discovery 2 (2016): 16028.
• Zaretsky, Jesse M., et al. "Mutations associated with acquired resistance to PD-1 blockade in melanoma." New England Journal of Medicine 375.9 (2016): 819-829.
• Müller, Judith, et al. "Low MITF/AXL ratio predicts early resistance to multiple targeted drugs in melanoma." Nature communications 5 (2014): 5712.