Table 1. Small molecules that have entered clinical trials (phase I, II and III) and their effects on overall survival (OS), median disease-free progression (mPFS), median overall survival (MoS) and outcomes of the trial where known. Compounds aligned as either monotherapy or combination therapy.
| Pancreatic cancer monotherapy | ||||
| Compound | Target | Survival | Comment | Ref. |
| Gemcitabine (1) | Thymidylate synthase and dihydrofolate reductase | MoS 5.6 months | 3 | |
| 5-FU (2) | Thymidylate synthase | MoS 4.4 months | 3 | |
| Nab-paclitaxel (3) | Topoisomerase I | MoS 8.5 months | ||
| PF-562271 (7) | Focal adhesion kinase and pyruvate kinase 2 | Generally well tolerated and most adverse events were of grade 1 or 2 and reversible | 31 | |
| LB-100 (8) | Protein phosphatase 2A | Continued development alone and in combination with other therapies | 32 | |
| CI-1040 (10) | Mitogen-activated protein kinase | Well tolerated and both target suppression and anti-tumour activity were demonstrated in this phase I study | 33 | |
| Selumetinib (35) | Mitogen-activated protein kinase | MoS 5.4 months | No statistical benefit over gemcitabine monotherapy | 55 |
| Marizomib (11) | Proteasome | 61% of evaluable patients demonstrated stable disease with 39% having decreases in tumour measurements. | 34 | |
| Salirasib (12) | RAS signalling pathway | MoS 6.2 months | The combination of gemcitabine and salirasib appears well-tolerated. | 35 |
| Pazopanib (18) | VEGFR tyrosine kinase | mPFS 25 monthsMoS 14.4 months | 40 | |
| Vatalanib (19) | Polytyrosine kinase | MoS 6 months | 41 | |
| Hydroxychloroquine (21) | Autophagy | MoS 23.3 months | 43 | |
| Vismodegib (29) | Hedgehog signalling pathway | MoS 6.9 months | No statistical benefit over gemcitabine monotherapy | 50 |
| Dactolisib (30) | Phosphatidylinositol 3-kinase and the mammalian target of rapamycin | Poorly tolerated by patients in phase II study | 51 | |
| PX-12 (32) | Proto-oncogene thioredoxin | mPFS 0.9 months | Trial terminated | 52 |
| MoS 3.2 months | ||||
| Veliparib (33) | Poly (ADP ribose) polymerase | mPFS 1.7 months | No statistical benefit over gemcitabine monotherapy | 53 |
| MoS 3.1 months | ||||
| Erlotinib (25) | EGFR Tyrosine kinase | Approved by the FDA for treatment of locally advanced, unresectable, or metastatic pancreatic cancer in 2005 | 60 | |
| Sunitinib (41) | VEGFR and PDGFR tyrosine kinase | Approved to treat patients with progressive, well-differentiated pNETs in 2011 | 61 | |
| Pancreatic cancer combination therapy |
||||
| FOLFIRINOX | Thymidylate synthase, dihydrofolate reductase, Topoisomerase and DNA | MoS 11.1 months | 16 | |
| Vorinostat (13) + capecitabine (17) | Histone deacetylase | MoS 13 months | 36 | |
| Pimasertib (14) + gemcitabine (1) | Mitogen-activated protein kinase | MoS 7.3 months | No clinical benefit with 7.6 month placebo group survival | 37 |
| Trametinib (34) + gemcitabine (1) | No statistical benefit over gemcitabine monotherapy (phase II) | 54 | ||
| Saridegib (16) + FOLFIRINOX | Hedgehog signalling pathway | Study closed early | 39 | |
| Galunisertib (20) + gemcitabine (1) | Transforming growth factor-beta receptor serine/threonine kinase | MoS 8.9 months | 42 | |
| Lapatinib (22) + capecitabine (17) | HER2/neu and EGF receptor tyrosine kinase | mPFS 2.6 months | Progressive disease | 44 |
| Progressive disease | ||||
| MoS 5.2 months | ||||
| Stable disease | ||||
| mPFS 4.0 | ||||
| MoS 8.3 months | Stable disease | |||
| Vandetanib (23) + gemcitabine (1) | VEGFR2, RET, and EGFR tyrosine kinase | MoS 8.8 months | MoS of 9.0 months in the vandetanib group and in the placebo group | 45 |
| Sorafenib (24) + erlotinib (25) | VEGFR tyrosine kinase | Failed to meet the primary end point | 46 | |
| Axitinib (38) + gemcitabine (1) | Failed to meet endpoints (phase III) | 59 | ||
| Dasatinib (26) + gemcitabine (1) | SRC (a non-receptor tyrosine kinase protein) and ABL receptor tyrosine kinases | No statistical benefit over gemcitabine monotherapy | 47 | |
| Saracatinib (27) + gemcitabine (1) | SRC receptor tyrosine kinases | No statistical benefit over gemcitabine monotherapy | 48 | |
| Imatinib (28) + gemcitabine (1) | PDGFR tyrosine kinase | mPFS 3.9 months | No statistical benefit over gemcitabine monotherapy | 49 |
| MoS 6.3 months | ||||
| Rigosertib (36) + gemcitabine (1) | Polo-like kinase 1 and phosphoinositide 3-kinase | MoS 6.1 months | Failed to demonstrate an improvement in survival with MoS 6.4 months with gemcitabine monotherapy | 56 |
| Olaparib (37) + irinotecan (5) + cisplatin (39) | Poly (ADP ribose) polymerase | Significant toxicity, trial terminated | 58 | |