protocols for cytotoxic anticancer agents pre-clinical evaluation

Dear all,
This is not Flow related question, but I need your kind help. Any suggestions will highly be appreciated.


 

I am planning to do cytotoxic anticancer
agents pre-clinical evaluation. From DTP website, I saw that they have
mentioned the procedures and guidance both in vitro and in vivo screen. Most of
the contents are from the book named “Anticancer Drug Development Guide:
Preclinical Screening, Clinical Trials, and Approval, Chapter 7, 2nd Ed., 2004,
Edited by Teicher, B.A. and Andrews, P.A., Humana Press Inc., Totowa, NJ.” I
read this book and still have many questions relating to detailed procedures.
Please do me a favor to guide me for the following questions.

 

1.      
If we plan to file the IND to FDA, normally how many cell lines do we
use in vitro study and how
many tumor models in vivo?

2.      
For in vitro study, there is NCI 60 cell lines, do we
need to test our compound in all of these cell lines or only we choose some
from each of the origins like 2 from colon, 2 from CNS, 2 from leukemia, 2 from
lung, 2 from mammary, 2 from melanoma, 2 from ovarian, 2 from prostate and 2
from renal?

3.      
For in vitro study, after the test,
we calculated the IC50, what is the threshold for further
evaluation with HFA and in vivo study.(I mean the IC50 should in mM or mM range that we can judge it
as potential )

4.      
For
in vivo study, should we only do human tumor xenograft
models in nude mice or, can we use rodent tumor models?

5.      
In human tumor xenograft models
with solid tumors in nude mice, where should we inoculate the tumors? Implanted
sc into the axillary region or ip-implanted?

6.      
In which condition can we use
ip-implanted model? If we use ip-implanted model, what should we use for drug
administration route? ip administration or iv administration?

 

 

I appreciate your kind reply.

 

Sincerely yours

 

Meixia Zhang