SUMOylation inhibitors for acute myeloid leukaemia (AML)

Maria Lois

CRAG, Centro de Investicación Agrigenómica UAB, Spain

Research
Cancer has a major impact on society worldwide. Although significant survival improvements have been achieved for some cancers, there is a serious need for novel therapeutic strategies to improve survival of others, such as Acute Myeloid Leukaemia (AML). AMLs are severe haematological malignancies leading to bone marrow failure and related complications. The inhibition of SUMO conjugation has emerged as a novel target for developing a new generation of anti-cancer therapies.

Aim
To generate a new family of SUMO conjugation inhibitors that will offer an effective therapeutic choice for AML patients who are not good candidates for receiving available chemotherapy.

Problem to Solve
The standard treatment for AML relying on conventional cytotoxic agents has remained almost unchanged for more than 40 years. In addition, elderly patients and those with relapsed AML are often not eligible for bone marrow stem cell transplants or the available aggressive cytotoxic treatments, constituting an unmet medical need. Recently, inhibition of SUMO conjugation has been identified as a valuable therapeutic strategy for those patients. However, the SUMO conjugation inhibitors identified display poor pharmacological properties, limiting their transfer to clinical treatments. It is extremely important to generate a novel family of inhibitors with high specificity, potency and low toxicity.

Innovation
Defects in SUMO conjugation are associated with cancer and SUMOylation inhibition is considered a new target therapy for treating AML, along with other cancer types. Based on fundamental research, a new molecular target for generating SUMO conjugation inhibitors has been identified, consisting on the disruption of protein-protein interactions rather than single enzymes. High-throughput screenings have identified peptides as alternative to complex natural products as therapeutic agents.

Level of Innovation
Inhibition of SUMO conjugation as therapeutic strategy by targeting protein-protein interactions based on inhibitory peptides, which provide better inhibition properties in terms of efficiency and low toxicity.