Table 2 Proof of concept in animal models for therapeutic benefit of reduction of DNM2

Prostate

Implantation of tumor cells (PC3, LNCaP, and C4-2) in prostate of male SCID mice

Stable expression of DNM2-siRNA or scrambled-siRNA in injected cells

9 weeks after cell injection:

 • Decrease in tumor weight

 • Reduction of number of lymph node metastases (for the PC3 cells able to induce metastases)

[36]

Prostate

Subcutaneous injection of PC3 cells in athymic mice

Pharmacological inhibitor (DBHA). Intratumoral injection in tumors of 7–13 mm

 • Reduction of the tumor volume at day 4 and day 8 after injection (vs vehicle injected tumors)

 • No apparent toxic effect at the necropsy (day 8)

[89]

Pancreas

Implantation of tumor cells overexpressing DNM2 or phospho-deficient DNM2 (PxPC-3) in pancreas of nude mice

Stable expression of WT DNM2-GFP or phospho-deficient DNM2-GFP in injected cells

2 weeks after cell injection:

 • Comparable size of primary tumor

 • Expression of the phospho-deficient mutant limits the distal dissemination of tumor cells from the injection area (vs WT DNM2-expressing cells)

8 weeks after cell injection:

 • Similar volume of the primary pancreas tumors

 • Large tumors in the body cavity

 • Expression of the mutant DNM2 decrease the number of large intestinal tumors vs WT DNM2-expressing cells

 • No liver tumors after injection of cells expressing the mutant (which occurs in 3 of 18 mice injected with cells overexpressing WT DNM2)

[42]

Breast

Injection of tumor cells expressing inducible DNM2 shRNA (MDA-MB-231-BR3) into mammary fat pads of nude mice

Doxycycline-inducible shRNA against DNM2 and control shRNA in injected cells

 • No decrease in tumor volume alone

 • Improvement of the tumor volume reduction induced by chemotherapy by cyclophosphamide

[41]

Glioblastoma

Injection of tumor cells (LN444/PDGF-A) into the brain of mice

DNM2-siRNA or control-siRNA in injected cells

8 weeks after cell injection:

 • Suppression of the PDGFRα–stimulated glioma growth (tumor volume) and invasion (number of prodruded fingers from tumors)

 • Decrease in tumor cell proliferation

 • Increase in cell apoptosis

[60]

Glioblastoma

Injection of tumor cells (GSC#035 with stable expression of luciferase) into the brain of nude mice

Continuous release of a DNM2 inhibitor (CyDyn 4–36) for 14 days by subcutaneous osmotic minipumps once tumors were established

Luciferase in vivo imaging after 1, 4, 8, 11 and 14 days of treatment:

 • Reduction of tumor volume statistically significant from 11 days of treatment (vs vehicle treated mice)

[82]

Leukemia

6-week-old Lmo2^Tg mice

IP injection twice daily for 5 days on 2 consecutive weeks of a DNM2 inhibitor (Dynole 34–2)

After 2 weeks of treatment:

 • Reduction in the number of DN3a thymocytes

 • Decrease in pre-LSC frequency

 • Progressive exhaustion of pre-LSCs

In non-tumour-bearing control mice: no detrimental effect of treatment on differentiated cells in the thymus and the bone marrow or the number of phenotypic bone marrow stem and progenitor cells

[90]

Leukemia

Injection of immature (ETP12) and mature (ALL8) T-ALL cell lines in mice

IP injection twice daily for 5 days on 2 consecutive weeks of a DNM2 inhibitor (Dynole 34–2). Treatment started when the average proportion of leukemic cells in the peripheral blood reached 1%

 • Increased survival of treated mice

24 h after the last administration:

 • Reduction in leukemic cells in the peripheral blood, bone marrow and spleen

 • Inhibition of the abnormally activated IL-7 and NOTCH1 signaling pathways in leukemic cells

[90]

Leukemia

Injection of AML cell lines AML01-307 and AML18) in immunodeficient mice

IP injection twice daily for 5 days on 2 consecutive weeks of a DNM2 inhibitor (Dynole 34–2)

 • Delayed onset of the disease

 • Increased survival of treated mice

24 h after the last administration:

 • Inhibition of IL-3, GM-CSF and SCF signaling pathways in leukemic cells

 • Less patient-derived AML cells in bone marrow and spleen of treated mice

[90]