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Pioneer: New Approach to Cancer Treatment

Conquest - Summer 2011

Mendelsohn helps pave the way 
for personalized therapies

By Scott Merville

In the 1980s, John Mendelsohn, M.D., and his colleagues took advantage of new discoveries and laboratory research tools to develop one of the first approaches to targeted cancer therapy.

Soon, he returns to research to help propel a highly personalized approach to cancer treatment, based on targeted drugs, from experimental or rare use into common practice.

“In the final endeavor of my academic career, I’m excited to participate in the effort to make personalized treatment become standard practice for our cancer patients,” Mendelsohn says.

When Mendelsohn and colleague Gordon Sato, Ph.D., set out to improve cancer treatment, drugs were blunt instruments that stymied reproduction of rapidly growing cells — both cancerous and normal.

The University of California at San Diego scientists decided to try something different by gumming up the connection between growth factors associated with cell reproduction and their receptor, found in abundance on some cancer cells.

“To put it most simply, we thought that if we were lucky, we could make an antibody to prevent that connection and block cell proliferation,” Mendelsohn says.

The arrival of C225

They identified one that did the trick. Moving the humanized version of the antibody, C225, into the clinic proved arduous.

“I have amazing memories of that time,” says José Baselga, M.D., Ph.D., then a fellow in Mendelsohn’s lab, which by then had moved to Memorial Sloan- Kettering Cancer Center in New York.

Erbitux is approved for colon 
and head and neck cancer 
Photo: F. Carter Smith

Baselga became hooked on Mendelsohn’s research while preparing to interview for that fellowship. Their discussion moved quickly to an exciting exchange “about experiments and things that needed to be done next,” Baselga recalls.

Baselga worked with Mendelsohn to complete the first clinical trial for C225, now called cetuximab, and preclinical work to try cetuximab with chemotherapy, among other projects.

All the while, Baselga notes, Mendelsohn led the Department of Medicine at Memorial Sloan-Kettering and was “beating on doors” to find companies to move.

Eventually, cetuximab advanced through a number of companies to emerge as Erbitux®, which is approved by the U.S. Food and Drug Administration for colon and head and neck cancer treatment.

“John moved science forward, but he also trained many guys like me, postdocs, how to analyze data, how to think,” Baselga notes.

Baselga is chief of the Division of Hematology/Oncology at Massachusetts General Hospital, one of the nation’s premier hospitals.

Mendelsohn is still moving the science forward.

© 2015 The University of Texas MD Anderson Cancer Center