Curis Hedgehog and Beyond --plus multi-targeting cancer inhibitors

The theory of Adult Stem Cells causing some/most cancers goes like this.

There is long-known association between cancer and chronic tissue injury. For example, if you stay out in the sun your are more likely to develop skin cancer. If you smoke you increase your risk for lung cancers. Another example is drinking. Continued chemical insult can also cause many cancers or even environmental factors.

How does this relate to ASC?

Every time your tissue ...

There are three main focuses of research surrounding the Hh pathway that could become relevant in a clinical application

1) Embryonic Stem cells for regenerative medicine (agonist/antagonist)
2) Agonist (turns pathway on)---which encompasses, degenerative diseases, stroke, hair growth in the adult body
3) Antagonist (turns pathway off)----Cancer http://www.pathway2curis.com/the-hedgehog-pathway-and-its-cancers-f7.html

I will touch on the basics of each topic and in the science section of this forum you can dig into the details of each one.

1) ...

CUDC-305 demonstrated high potency in vitro and in vivo across a wide range of cancers. Most notably, Curis scientists observed complete tumor regression following oral administration of CUDC-305 in a mouse xenograft model of acute myelogenous leukemia(AML). Tumor regression has also been observed after treatment of CUDC-305 in mouse xenograft models of breast, non-small cell lung, gastric cancer and glioblastoma brain cancers. In this preclinical testing, the compound also demonstrated an ability to effectively cross ...

Advanced Solid Tumors
http://clinicaltrials.gov/ct2/show/NCT00880308?term=LDE225 PI
This first-in-human dose-escalation study is to characterize the safety, tolerability, pharmacokinetics and pharmacodynamics of LDE225 given orally on a daily dosing schedule in patients with advanced solid tumors.
Study Start Date: March 2009
Estimated Primary Completion Date: December 2010

Skin Basal Cell Carcinomas in Gorlin's Syndrome Patients PI / PII
http://clinicaltrials.gov/ct2/show/NCT00961896?term=LDE225
A double-blind, randomized, vehicle-controlled Proof of Concept (PoC) study to evaluate the safety, local tolerability, pharmacokinetics and pharmacodynamics of ...

Advanced and/or Metastatic Solid Tumor Malignancies PI
http://clinicaltrials.gov/ct2/show/NCT00761696?term=IPI-926
A Phase 1 Study of IPI-926 in Patients With Advanced and/or Metastatic Solid Tumor Malignancies

http://clinicaltrials.gov/ct2/results?term=IPI-926

Mutation Driven

• Rhabdomyosarcoma
• Medulloblastoma
• Nevoid Basal Cell Carcinoma Syndrome (NBCCS)
• Basal Cell Carcinoma
• Gorlin Syndrome

Ligand Driven

• Breast Cancer
• Esophageal Cancer
• Gastric Cancer
• Glioblastoma
• Pancreatic Cancer
• Prostate Cancer
• Small-Cell Lung Cancer (SCLC)
• Colon Cancer

CUDC-101 is a molecule that can target 3 different and novel cancer pathways at once. This allows patients to take a single doses instead of having to take multiple agents at once or at various times. The intent of this design is for network disruption.

• Efficacy dose ranges are above 150mg/m2
• About double the half life in tumors when compared to plasma

What does CUDC-101 Target? (EGFR, HDAC, HER2)

EGFR (Epidermal growth factor receptor) ...

Hedgehog Inhibition for Pancreatic Ductal Adenocarcinoma (PDAC) in the Preoperative Setting (HIPPoS)

http://www.clinicaltrials.gov/ct2/show/NCT01096732?term=GDC-0449
Purpose
This clinical trial is looking at the effect of a new drug called GDC-0449 in patients with cancer of the pancreas. Laboratory studies have shown that this drug blocks a process in pancreatic cells thought to be involved in cancer development and spread. This process is called the 'Hedgehog signalling pathway'. As yet, it is unclear whether blocking hedgehog signalling will ...

Chronic Myeloid Leukemia (CML) Phase I
http://clinicaltrials.gov/ct2/show/NCT00953758?term=PF-04449913
This study examines the effect of a small molecule inhibitor to the Sonic Hedgehog pathway on select hematologic malignancies. Part two of the study will examine the effect of this inhibitor in combination with dasatinib.

Study Start Date: January 2010
Estimated Study Completion Date: April 2013


http://clinicaltrials.gov/ct2/results?term=PF-04449913

Extensive-Stage Small Cell Lung Cancer Phase I
http://clinicaltrials.gov/ct2/show/NCT00927875?term=BMS-83392
The purpose of this study is to determine the maximum tolerated dose (MTD) of BMS-833923 administered in combination with carboplatin and etoposide followed by BMS-833923 alone in subjects with extensive-stage Small Cell Lung Cancer (SCLC).

Study Start Date: December 2009
Estimated Study Completion Date: July 2011

Metastatic Gastric, Gastroesophageal, or Esophageal Adenocarcinomas Phase I
http://clinicaltrials.gov/ct2/show/NCT00909402?term=BMS-833923
The purpose of this study is to determine the maximum tolerated dose ...