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. 2021 Dec 27;23(1):262. doi: 10.3390/ijms23010262

Table 2.

Role of PDE5 inhibitors (PDE5i) in several cancer types, and related clinical trials.

Cancer Type Role of PDE5i References PDE Inhibitor Clinical Trial.Gov
Breast
  • -

    Apoptosis

  • -

    ROS generation

  • -

    Enhancement of cisplatin-induced apoptosis

  • -

    EPR augmentation

  • -

    Enhancement of antitumor immune response

  • -

    Down-regulation of oncogenic Wnt/β-catenin pathway

  • -

    Improvement in anticancer drug concentration

  • -

    Chemoprevention

 [51,64,74,88,89] Sildenafil (PDE5i) NCT01375699
Pentoxifylline (non-specific PDEi) NCT03916068
NCT02898376
NCT00022204
NCT00188669
NCT01082003
NCT00583700
Colon
  • -

    Apoptosis

  • -

    ROS generation (down-regulation of MCL-1, BCL-XL, thioredoxin and SOD2

  • -

    Alteration of normal epithelium (reduction in the proliferative compartment in the colon)

  • -

    Suppression of inflammation

  • -

    Chemoprevention

 [103,104,105,106] Udenafil (PDE5i) NCT00607282
Hepatoma
  • -

    Enhancement of the therapeutic efficacy of BET inhibitors via Hippo pathway

  • -

    Restoration of antioxidant enzymes

  • -

    Enhancement of anti-tumor immune activity

 [107,108,109] Tadalafil (PDE5i) NCT03785210
Pentoxifylline (non-specific PDEi) NCT01149304
Leukemia
  • -

    Apoptosis

  • -

    Potentiation of chemotherapeutic-induced apoptosis

 [110,111] Sildenafil, Tadalafil,
Vardenafil (PDE5i)		 NCT01117142
Pentoxifylline (non-specific PDEi) NCT02451774
Theophylline (PDE3i-PDE4i) NCT00003808
Lung
  • -

    Apoptosis

  • -

    EPR augmentation

  • -

    Reduction of cancer stemness

  • -

    Potentiation of chemotherapy

  • -

    Sensitization of tumor cells to apoptosis

 [51,112,113] Papaverine hydrochloride (PDE10i)
Sildenafil (PDE5i)		 NCT03824327
Pentoxifylline (non-specific PDEi) NCT00752115
Theophylline (PDE3i-PDE4i)
Tadalafil (PDE5i)		 NCT01871454
Caffeine (non-specific PDEi) NCT01799161
NCT02080078
NCT04069936
NCT01402089
Lymphoma
  • -

    Inhibition of romidepsin-induced EBV reactivation

  • -

    Increase of brain vascular permeability to anticancer drugs

 [114,115] Sildenafil, Tadalafil,
Vardenafil (PDE5i)		 NCT01117142
Pentoxifylline (non-specific PDEi) NCT02451774
Ovarian
  • -

    Enhancement of anti-tumor immunotherapy

  • -

    Suppression of chemotherapy resistance through reduction of ABC drug efflux pumps ABCB1 and ABCG2

 [94,116] Caffeine (non-specific PDEi) NCT04718740
Dipyridamole (PDE3i) NCT00002487
Prostate
  • -

    Ameliorates biochemical recurrence-free and overall survival

  • -

    Regulation in androgen receptor expression and aromatase activity

  • -

    Enhancement of anticancer drug-mediated tumor growth arrest (in combination with vincristine, docetaxel)

 [117,118,119,120,121] Sildenafil (PDE5i): NCT00906269
NCT00142506
NCT01996852
NCT01054001
Tadalafil (PDE5i): NCT00931528
NCT00215631
NCT00122499
Udenafil (PDE5i): NCT03142542
Papaverine hydrochloride (PDE10i): NCT00080808