Replies to post #121232 on Biotech Values

[NP1986]

Two points:

(1) Has it even been tested yet in patients who are not positive for EML4-ALK? How do we know that crizotinib's efficacy is limited to these patients?

(2) My main point is not that ALK is not a valid target, but when you have a drug that is targeting multiple pathways how exactly do you know how much antitumor activity is attributable to each pathway?

[biomaven0]

No, NP1986 has a valid point - if the drug has two targets then one can't be sure in general which one (or even the combination) is the key to a particular response.

In fact here is this brand-new abstract:

J Thorac Oncol. 2011 May;6(5):942-946.
Activity of Crizotinib (PF02341066), a Dual Mesenchymal-Epithelial Transition (MET) and Anaplastic Lymphoma Kinase (ALK) Inhibitor, in a Non-small Cell Lung Cancer Patient with De Novo MET Amplification.
Ou SH, Kwak EL, Siwak-Tapp C, Dy J, Bergethon K, Clark JW, Camidge DR, Solomon BJ, Maki RG, Bang YJ, Kim DW, Christensen J, Tan W, Wilner KD, Salgia R, Iafrate AJ.
Source
*Chao Family Comprehensive Cancer Center, University of California Irvine Medical Center, Orange, California; †Massachusetts General Hospital Cancer Center, Boston, Massachusetts; ‡University of Colorado Cancer Center, Aurora, Colorado; §Peter MacCallum Cancer Center, Melbourne, Australia; ?Melanoma Sarcoma oncology, Memorial Sloan Kettering Cancer Center, New York City, New York; ¶Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea; #Pfizer Global Research and Development, La Jolla, California; **University of Chicago, University of Chicago Medical Center, Chicago, Illinois; and ††Department of Pathology. Massachusetts General Hospital, Boston, Massachusetts.
Abstract
Crizotinib is a dual MET and ALK inhibitor. Currently, clinical development of crizotinib is focused primarily on ALK rearranged non-small cell lung cancer (NSCLC). Here we report an NSCLC patient with de novo MET amplification but no ALK rearrangement who achieved a rapid and durable response to crizotinib indicating is also a bona fide MET inhibitor.