Table 2

Specific therapies inducing/mitigating the development of an accelerated ageing-like state

Agent modalityAgentCellular effects
Radiotherapy
  • Ionising radiation

Cellular senescence, changes to DNA repair genes, epigenetic alterations
Hormonal
  • Tamoxifen

Cellular senescence
Tyrosine kinase inhibitors
  • Sunitinib

  • Dasatinib

Cellular senescence
Dasatinib→senolytic
Anthracyclines
  • Doxorubicin,

  • Daunorubicin

Free radical generation, DNA damage, telomere attrition, cellular senescence, stem cell exhaustion
Alkylating agents
  • Cyclophosphamide

  • Temozolomide

DNA damage, cellular senescence, epigenetic alterations
Topoisomerase inhibitors
  • Anthracyclines

  • Epipodophyllotoxin (eg, etoposide)

  • Camptothecin analogues (eg, irinotecan)

DNA damage, epigenetic alterations
Antimetabolites/cytotoxic drugs
  • 5-Fluorouracil

  • Cisplatin

Cellular senescence, DNA damage
BRAF inhibitor
  • Vemurafenib

Cellular senescence
Antitumor antibiotics
  • Mitomycin C

Cellular senescence, epigenetic alterations
Isoquinololine alkaloid
  • Berberine

Cellular senescence
Bcl-2 inhibitor
  • Navitoclax

  • Obatoclax

Senolytic (apoptosis of senescent cells)
HCT (includes conditioning regimen)
  • N/A

Telomere attrition, stem cell exhaustion
Telomerase inhibitors
  • GRN163L (Imetelstat)

  • Vaccines (GV-1001, GRNVAC1, Vx-001)

Possible telomere attrition
Nucleoside analogue reverse-transcriptase inhibitor
  • Azidothymidine

Telomere attrition
DNA cross-linking agents
  • Cisplatin

Epigenetic alterations
Ribonucleotide reductase inhibitors
  • Hydroxyurea

  • Methotrexate

Epigenetic alterations
Microtubule inhibitors
  • Vinca alkaloids (vinblastine, vincristine, vindesine, vinorelbine)

  • Taxanes (paclitaxel, docetaxel)

  • Podophyllotoxin

Epigenetic alterations
miRNA
  • miR-34a

  • miR-144

  • miR-21

  • miR-155

Cellular senescence, telomere attrition
GVHD
  • N/A

Telomere attrition
  • BRAF, B-Raf proto-oncogene; Bcl-2, B cell lymphoma 2; GVHD, graft-versus-host disease; HCT, haematopoietic cell transplantation; miRNA, micro RNA; N/A, not available.