Drug resistance in glioblastoma: are persisters the key to therapy?

Lisa Oliver; Lisenn Lalier; Céline Salaud; Dominique Heymann; Pierre François Cartron; François M Vallette

doi:10.20517/cdr.2020.29

Drug resistance in glioblastoma: are persisters the key to therapy?

Cancer Drug Resist. 2020 Aug 7;3(3):287-301. doi: 10.20517/cdr.2020.29. eCollection 2020.

Authors

Lisa Oliver^{1

2}, Lisenn Lalier^{1

3}, Céline Salaud^{1

2}, Dominique Heymann^{1

3}, Pierre François Cartron^{1

3}, François M Vallette^{1

3}

Affiliations

¹ Université de Nantes, INSERM, CRCINA, Nantes 44007, France.
² CHU de Nantes, Nantes 44093, France.
³ LaBCT, ICO, Saint Herblain 44805, France.

Abstract

Glioblastoma (GBM) represents the main form of brain tumors in adults, and one of the most aggressive cancers overall. The treatment of GBM is a combination of surgery (when possible), chemotherapy (usually Temozolomide, TMZ) and radiotherapy (RT). However, despite this heavy treatment, GBM invariably recur and the median length of survival following diagnosis is 12 to 15 months, with less than 10% of people surviving longer than five years. GBM is extremely resistant to most treatments because of its heterogeneous nature, which is associated with extreme clonal plasticity and the presence of cancer stem cells, refractory to TMZ- and RT-induced cell death. In this review, we explore the mechanisms by which cancer cells, and especially GBM, can acquire resistance to treatment. We describe and discuss the concept of persister/tolerant cells that precede and/or accompany the acquisition of resistance. Persister/tolerant cells are cancer cells that are not eliminated by treatment(s) because of different mechanisms ranging from dormancy/quiescence to senescence. We discuss the possibility of targeting these mechanisms in new therapeutic regimen.

Keywords: Drug resistance; chromatin remodeling; metabolism; persisters; tolerance; tumor environment.

Publication types

Review