3 u A b C A N C e r C e N T e r2 u A b C o m P r e H e N S I V e C A N C e r C e N T e r u A b C o m P r e H e N S I V e C A N C e r C e N T e r 3

B y J o s h T i l l

moSt PromiSiNg moNocLoNAL

ANtiBodieS deveLoPed At uAB iS

tigAtuzumAB, ALSo KNoWN AS trA-8. it WorKS By

tArgetiNg SPeciFic SiteS oN ceLL SurFAceS KNoWN

AS “deAth recePtorS,” triggeriNg ceLL deAth.

and some are the results of years of research.

But all are examples of UAB’s status as an

international leader in the fight against can-



For many years, the Cancer Center has

been recognized as a leader in the research

and development of monoclonal antibodies,

which are laboratory-produced molecules that

bind to specific proteins on the surface of

tumor cells and interfere with cell function.

One of the most promising of these has

been the monoclonal antibody tigatuzumab,

also known as TRA-8. Developed at UAB

by Cancer Center scientist Tong Zhou,

M.D., tigatuzumab works by targeting spe-

cific sites on cell surfaces known as “death

receptors,” triggering cell death. It was a

particularly exciting discovery because at the

time, not many believed an antibody could

directly induce cell death.

Tigatuzumab had previously shown prom-

ise in treating breast, colon, lung, pancreatic,

brain and prostate cancer in animal models.

Because of that, the antibody was moved

quickly into human trials. In 2010, the Cancer

Center launched the first trial of tigatuzumab

for patients with metastatic triple negative

breast cancer, which accounts for about 25

percent of all breast cancers and seems to

show the greatest response to tigatuzumab.

Much of the early work involving tig-

atuzumab was funded by the Birmingham-

based Breast Cancer Research Foundation

of Alabama. Further funding to continue

this work came in 2009 in the form of a

$6.4-million Promise Grant from the Susan

G. Komen for the Cure Foundation and the The UAB Comprehensive Cancer Center

was one of the first eight centers to receive

that prestigious designation, and since that

time, it has solidified its status as one of

the premier cancer centers in the United

States—and beyond.

While UAB’s cancer program took a

leap forward in 1968 with the Courage

Crusade—which followed the death of

Governor Lurleen Burns Wallace (see side-

bar on page 5)—the investment from the

National Cancer Act allowed the institu-

tion to become a major player in the war on


That investment—a $254,334 plan-

Triple Negative Breast Cancer Foundation.

“This antibody is a perfect example of

the UAB Comprehensive Cancer Center’s

strength in translating our laboratory dis-

coveries into treatments for our patients,”

says Cancer Center senior scientist Andres

Forero, M.D., principal investigator for

these studies. “It’s a major accomplishment

and incredibly exciting.”

REsEARCh IN REtINOIDs For more than 20 years, Cancer Center

senior scientists Donald Muccio, Ph.D., and

Wayne Brouillette, Ph.D., have been engi-

neering cancer-fighting retinoids derived from

vitamin A. Their laboratory has designed and

synthesized more than 100 such compounds

and patented many of these novel molecules.

One of the most promising of these

compounds is UAB-30, which was selected

for further tests by the NCI’s RAPID

(Rapid Access to Preventive Intervention

Development) program to determine its

safety, toxicity and pharmacology prior to

developing initial clinical trials.

Retinoids fight cancer in three ways: by

controlling cell growth, by controlling dif-

ferentiation to keep cells in a normally func-

tioning state and by controlling apoptosis (cell

death). UAB-30 was chosen for the RAPID ning grant from the National Cancer

Institute—has paid off. Today, the UAB

Comprehensive Cancer Center is home to

more than 350 scientists and physicians,

and it generates more than $100 million

in research support from outside sources.

It remains the only comprehensive cancer

center in Alabama as well as in the six-state

region of the Deep South that stretches

from South Carolina to Louisiana and


This issue of UAB Comprehensive Cancer

Center celebrates the Comprehensive Cancer

Center’s 40th anniversary by highlighting

some of its top discoveries. Some are recent,

In 1971, President Richard M. Nixon signed the National Cancer Act, a revolutionary piece of

legislation that designated federal money for cancer research, treatment and education. It also

established the “comprehensive” cancer center designation for institutions that provided the

most advanced cancer care, research and education based on stringent peer-reviewed criteria.

C A N C e R C e N t e R t I M e l I N e

Death of Governor lurleen b. Wallace from cancer initiates statewide fundraising drive known as the Courage Crusade.

uAb cancer program organized, with Dr. John Durant appointed as director. Courage Crusade raises $5 million and,

with additional funds from the National Cancer Institute, allows construction of the Wallace Tumor Institute and Wallace Patient Tower at uAb Hospital.

uAb established as one of the first eight comprehensive cancer centers by the National Cancer Act.

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of Discoveries: Four Decades

One OF the