Editor: Heike Chauvisté, A11

Date: 12/06/2022

Melanoma is a highly dynamic tumor. Dormant phases and active cell division can quickly alternate. Some melanoma cells are in a rather slow cycling state and do not seem to contribute significantly to cancer growth. However, these are cells of the so-called persister type, which often only switch to active cell division during cancer treatment. Therefore, work from A11 (Roesch), A06 (Ehrmann), B01 (Kaiser) and Z03 (Kaschani) have successfully tested a new strategy in laboratory experiments and recently published it in the prestigious journal "Nature Communications". Using a new active substance, they were able to keep the persister cells in the resting phase in a cell culture model and thus make these cells vulnerable to drug treatment.

"By moving from dormancy to active cell division, these persister cells escape most cancer drugs. They cause the relapse through enhanced regrowth," explains the corresponding author Prof. Dr. Alexander Roesch from the Clinic for Dermatology at the University Medical Centre Essen. What characterises these persister cells at the molecular level, and how the switch between activity and dormancy can be prevented is what he and his research team from KFO 337 "PhenoTImE" and cooperating working groups of SFB 1430 have now investigated in more detail.

The researchers discovered the protein KDM5B in the persister cells. When it is particularly active, the cells remain in the resting phase. The researchers believe: "In order to be able to maintain long-term tumor growth, melanoma cells have to leave the high activity level of KDM5B again." The researchers now prevented this flexibility in the laboratory by using the compound Cpd1. They observed another promising effect: under the influence of Cpd1, an additionally administered anti-cancer drug was able to unfold its full effect. "This double-strike strategy could become a major advance for cancer therapy. However, the next step must first be to test and hopefully confirm our findings in clinical practice," says Prof. Roesch.

Publication:

Chauvistré H, Shannan B, Daignault-Mill SM, Ju RJ, Picard D, Egetemaier S, Váraljai R, Gibhardt CS, Sechi A, Kaschani F, Keminer O, Stehbens SJ, Liu Q, Yin X, Jeyakumar K, Vogel FCE, Krepler C, Rebecca VW, Kubat L, Lueong SS, Forster J, Horn S, Remke M, Ehrmann M, Paschen A, Becker JC, Helfrich I, Rauh D, Kaiser M, Gul S, Herlyn M, Bogeski I, Rodríguez-López JN, Haass NK, Schadendorf D, Roesch A.
Persister state-directed transitioning and vulnerability in melanoma.
Nat Commun. 2022 Jun 1;13(1):3055.

Link to the publication