Project for effectual therapy of Neuroblastoma

1. Functional Characterization of Muscarinic
Acetylcholine Receptors (mAchR) on
Neuroblastoma cells
Name: Arijit Bhowmik
Roll no. : 65
Course work batch: 2012-13
GRANT DEFENCE

2. What is neuroblastoma?
image adapted from O'Neill: Principles of Pediatric Surgery. © 2003, Elsevier.

3. Why we need to target
Neuroblastoma ?

4. Type of Neuroblastoma
Image taken from http://bmi.osu.edu/cialab/neuro_project.php

5. Pathways associated with
Neuroblastoma progression
 EGFR, IL6, VEGF, NGF, Notch, STAT-1 , Sonic
hedgehog signaling
 Along with these upregulation of N-Myc in this type of
cancer is very common

6. Synaptogenesis
V. Vetri, R. Carrotta, P. Picone, M. Di Carlo, V. Militello. Biochim. Biophys. Acta - Protein & Proteomics 1804, (2010) 173-183.

7. Presence of mAchR in neuronal cells

8. mAchR is a GPCR receptor
• Amanita muscaria, the mushroom from which
muscarine was isolated.
• These receptors are sensitive to this
compound. Thus it is known as Muscarinic
Acetylcholine Receptors (mAchR)

9. G protein-coupled receptors
(GPCR) comprise the largest
family of drug targets
The 2012 Nobel prize in chemistry was awarded to Brian Kobilka and Robert Lefkowitz
for their work that was "crucial for understanding how G-protein–coupled receptors
function.
Brian Kobilka Robert Lefkowitz

11. Muscarinic acetylcholine receptor pathway
Drug News Perspect 2004, 17(4): 258

12. GPCR receptors have crosstalk with
the major oncogenic signaling
pathways
So in our proposal we have predicted that Muscarinic Acetylcholine
Receptors (mAchR) and its related pathway could be a possible
mediator of oncogenic crosstalks in neuroblastoma

13. The study will mainly focus on……
 Quantitative in situ assessment of mAchR in different grades of
neuroblastoma samples.
 Role of mAchR in progressive neuroblastoma occurrence and
its effect on proliferation or apoptosis.
 The possible existence of cross talk of mAchR and its pathway
members with other key signaling molecules affecting the
occurrence of malignant neuroblastomas.

14. In Summary…….
 Neuroblastoma is a disease exhibiting extreme
heterogeneity.
 Therapy for high-risk neuroblastoma the past two decades
resulted in cures only about 20% of the pateint population.
 Targeting mAchR in neuroblastoma may generate new
avenues in molecular biology and therapeutic strategies.
 Thus novel drugs will be inducted into clinical practice
guidelines of high grade neuroblastoma treatment.