Biology Reference
In-Depth Information
Table 5.1
Clinical Trials of SMO Inhibitors
SMO Inhibitor
Tumour Type
GDC-0449
Phase II BCC, pancreatic, ovarian, lung,
gastric colorectal, medulloblastoma
Phase I breast
LDE225
BCC
Medulloblastoma
Lung adenocarcinoma, spindle cell sarcoma,
breast cancer
IPI-926
BCC, chondrosarcoma
IPI-926+
Gemcitabine
Metastatic pancreatic cancer
IPI-926+ leucovorin
IPI-926+ Cetuximab
Metastatic pancreatic cancer
Recurrent head and neck cancer
BMS-833923 (XL139)
BMS+ lenalidomide + dexamethasone,
bortezomib
BCC, advanced or metastatic solid tumours
refractory to standard therapy
Refractory multiple myeloma
BMS+ Dasatinib
BMS+ Cisplatin; Capecitabine
Leukaemia
BMS+ Carboplatin+ Etoposide
LEQ506
Metastatic gastric, gastroesophageal,
osophageal adenocarcinomas
Small cell lung carcinoma
TAK-441
Advanced solid tumours, recurrent or
refractory medulloblastoma, locally
advanced or metastatic BCC
Non-haematologic malignancies; BCC
Source
: Data collated from
www.clinicaltrials.gov
and from references given in the text.
regulator of hedgehog signaling, by SAHA and accentuated downregulation repres-
sion of PTCH-1 mRNA expression (Chun et al., 2009).
Numerous clinical trials are being carried out with HDAC inhibitors on their own
or in combination with other agents), which are not enumerated in
Table 5.1
or dis-
cussed here for the focus is on HDAC inhibitors that potentiate the effects of inhibi-
tors of SMO function. The current or completed clinical trials are listed in
Table 5.1
,
which is based on the information collated from
www.clinicaltrials.gov
.
Targeting Gli1 in Deregulated Hh Signalling
As discussed earlier, SMO is an important element to target in negating deregulated
Hh signalling encountered in cancer. Downstream of SMO is the transcription fac-
tor Gli1 whose activity is regulated by SMO. Of course other G-proteins are known
to activate it quite independently of SMO. Indeed, several G-proteins possess the
Search WWH ::
Custom Search