Download Research in Radiation Oncology at University of Texas M. D.

Research in Radiation Oncology at University of Texas M. D. Anderson Cancer Center: From the
Laboratory to the Clinic
Luka Milas, M. D., Ph. D., Division of Radiation Oncology,The University of Texas M. D. Anderson Cancer Center,
Houston, Texas, USA
The University of Texas M. D. Anderson Cancer Center (MDACC) is one of the premier cancer centers in the
United States of America (USA) and in the world. Its mission is to eliminate cancer in Texas, USA and the world
through outstanding integrated quality programs in patient care, research, education and prevention. MDACC has
more than 17,000 employees, including more than 1,500 faculty members. It has more than 5,000 trainees, and
its excellence in research is exemplified by having received more peer-reviewed grants from the National Cancer
Institute than any other academic institution in the USA. Among many of its research and clinical divisions and
departments is the Division of Radiation Oncology, the largest of its kind in the world. It is composed of three
separate departments: Radiation Oncology, Experimental Radiation Oncology and Radiation Physics. The
mission of the Division of Radiation Oncology is to provide the most compassionate, technologically advanced
and efficient radiation treatment of cancer patients; to integrate developments from biology and physics with
clinical research and to improve patient outcomes; and to educate future generations of physicians, scientists and
allied health professionals to become leaders of their disciplines.
The research in the Division of Radiation Oncology strives to (1) improve the quality and therapeutic ratio of
radiation therapy through research aimed at innovations in imaging, treatment design, and delivery methods; (2)
improve the conformance of radiation treatments to targeted regions, such as the use of proton therapy, thereby
minimizing dose delivered to normal tissues; (3) enhance the probability of radiation cell kill of tumors by
selectively enhancing the radiosensitivity of tumor cells through combination therapies with chemotherapy and/or
molecular targeted therapies; and (4) understand molecular mechanisms of tumor cell resistance to radiation and
develop strategies to overcome this resistance. Many tumor cell, microenvironment and host factors determine
tumor radioresponsiveness, including the presence of a subpopulation of cells within tumors, so-called cancer
stem-like cells, which is uniquely capable of re-establishing the tumor during and after definitive treatment. It is
becoming increasingly appreciated that these cancer stem-like cells must be effectively controlled to achieve a
long-term cure. The existence and physiology of a rare cancer cell sub-population, termed cancer cell clonogens,
with similar properties to the cancer stem-like cells has been extensively described in the radiobiology literature
for several decades. These earlier studies have identified important features that govern tumor establishment;
tumor growth and homeostasis; and therapeutic resistance mechanisms, including clonogen number, tumor type,
vascular status, hypoxia, cell repopulation dynamics during treatment, and immunologic and micro-environmental
status. These discoveries led to therapeutic strategies, some of which have shown efficacy and have become
current standard clinical practice (for example, concomitant boost and concurrent radio[chemo]therapy). Although
the identity of cancer stem-like cells and cancer cell clonogens has not been definitively shown, recent
characterization of molecular signaling pathways controlling stem cells and their microenvironmental niche
combined with the earlier findings on clonogen physiology may now lead to the development of molecularly
targeted strategies to overcome therapeutic resistance of this rare sub-population of tumor cells. Along these
lines, we are currently exploring unique treatment settings (ie, before, during, and after definitive radio [chemo]
therapy) in which molecularly targeted approaches might specifically counteract cancer stem-like cell resistance
mechanisms and enhance the curative efficiency of radio(chemo)therapy.
The study of cancer stem-like cells is
one of many examples that illustrate the complementary interplay between basic, translational and clinical
research in the MDACC Division of Radiation Oncology aimed at improving therapeutic ratio of radiation therapy.