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. 2015 Feb 9;17:e5. doi: 10.1017/erm.2015.3

Table 2.

Examples of preclinical combination studies of SMO inhibitors and other agents

Inhibitors (target) Indication Effects in preclinical study References
HHi + RAS/RAF/MEKi
Cyclopamine + U0126 (MEK)/SH6 (AKT) Melanoma Combination synergistically reduces cell growth in vitro (78)
Cyclopamine + U0126 (MEK) Cholangiocarcinoma Additive antiproliferative effect (275)
HHi + EGFRi
Cyclopamine + Gefitinib Pancreatic cancer Combination decreases cell viability in vitro and tumour growth in vivo (276)
Cyclopamine + Gefitinib + Docetaxel Prostate cancer Combination decreases tumour growth and invasion in vitro (277)
Cyclopamine + Erlotinib GBM Combination decreases tumour sphere formation (278)
Saridegib + Cetuximab HNSCC Combination abrogates tumour growth in vivo (279)
HHi + PI3K/mTORi
Sonidegib + Buparlisib (PI3K) or BEZ235 (PI3K/mTOR) MB Combination delays resistance observed with sonidegib alone (254)
Sonidegib + Buparlisib (PI3K) GBM Combination synergistically reduces tumour growth in vitro and in vivo (280)
Cyclopamine or CUR199691 + Rapamycin (mTOR) + Gemcitabine Pancreatic cancer Triple combination leads to CSC elimination in vitro and in vivo and increases survival (281)
Vismodegib + Everolimus (mTOR) Oesophageal adenocarcinoma Everolimus enhances vismodegib inhibition in vivo (41)
SIBI-C1 + Rapamycin (mTOR) + Gemcitabine Pancreatic cancer Triple combination eliminates CSC, reduces tumour growth in vivo and increases survival (282)
HHi + NOTCHi
Cyclopamine + GSI-XXI Leukaemia Combination inhibits growth in vitro (283)
Cyclopamine + MRK-003 GBM Combination decreases cell growth and increases apoptosis (218)
Cyclopamine + GSI-1 Glioma Combination enhances the effect of temozolomide (284)
Cyclopamine or Vismodegib + DBZ or compound E Prostate Combination depletes docetaxel-resistant prostate cancer cells in vitro and in vivo (285)
HHi + BCR-ABLi
Cyclopamine + Nilotinib CML Combination prolongs survival in mouse model (89)
Vismodegib + Dasadegib CML Combination enhances cytotoxicity (288)
Vismodegib + Ponatinib (pan-ABL) Leukaemia Combination leads to decreased CD19+ cells, overall tumour burden and increases survival (289)
HHi + others
Cyclopamine + Gemcitabine Pancreatic cancer Combination abrogates metastases and reduces primary tumours (71)
Saridegib + Gemcitabine Pancreatic cancer Saridegib facilitates gemcitabine delivery and extends survival (139)
Cyclopamine + Temozolomide GBM Combination synergistically reduces CSC proliferation in vitro (75)
SEN-450 + Temozolomide GBM Combination reduces tumour growth in vivo (290)
Sonidegib + VX-680 (Aurora kinase) or BI-2536 (Polo-like kinase) MB Combination reduces proliferation in vitro and in vivo (292)
Cyclopamine + CCT (WIP1) Melanoma, breast cancer Combination synergistically reduces tumour growth in vitro (215)

Abbreviations: CCT, CCT007093; CML: chronic myeloid leukaemia; CSC, cancer stem cells; GBM: glioblastoma; HNSCC, head and neck squamous cell cancer; MB, medulloblastoma.