Esther H. Chang, Ph.D.
Georgetown University
Washington, DC

Attacking Treatment-Resistant Cancer Cells

Cancer research efforts have traditionally followed a long, tortuous path from initial inception in the research lab to widespread clinical application. This circuitous route frequently requires researchers to clear strenuous but important hurdles before an untested treatment is ready for human trials. Even then, many conditions must be met before the new therapy becomes widely available to cancer patients.

So, when it comes to fighting devastating diseases like cancer, researchers are understandably seeking ways to safely expedite the route from bench to bedside.

Project Director Expertise

Esther Chang, PhD, a microbiologist at Georgetown University's Lombardi Cancer Center in Washington, D.C., has focused her research efforts on testing new therapies while administering existing, proven medications. By taking this novel and innovative approach, Dr. Chang speeds the clinical implementation of promising treatments while still offering patients tried-and-true care regimens.

NFCR Research Overview

First and foremost, Dr. Chang's research aims to enhance the usefulness of conventional radiation and chemotherapy treatments, which can lose their effectiveness as cancer cells become resistant to conventional protocols, or as tumors metastasize or spread to other parts of the body, making them difficult to locate and treat. To overcome these challenges, Dr. Chang has tried to pinpoint ways to make these resistant or metastatic cells more sensitive to radiation and chemotherapy.

To that end, her basic science research efforts have centered on gaining a better understanding of the genetic factors that lead to cancer. She has studied three different oncogenes-or tumor-causing genes-to find out what activates their cancer-causing ability.

She also focused on the p53 tumor suppressor gene to determine what stops its cancer-inhibiting ability. In addition, she has developed ways to deliver a healthy p53 gene that kills cancer cells or makes them more susceptible to standard radiation and chemotherapy treatments.

NFCR Research Findings

Dr. Chang has made significant inroads into understanding how oncogenes are formed. Oncogenes start out as proto-oncogenes, which are important regulators of cell growth and cell death in all people. Sometimes, however, proto-oncogenes mutate to become oncogenes, which allow cells to become malignant or cancerous.

When proto-oncogenes mutate, they produce a protein that allows tumor formation. Dr. Chang has discovered a specific agent, called an antisense oligonucleotide, which stops tumor proteins from forming. This agent also makes most tumor cells more sensitive to radiation or chemotherapy.

In other research, Dr. Chang has tested ways to deliver healthy p53 tumor suppressor genes to fight cancer in mice with damaged p53 genes. Given in combination with radiation treatment, the healthy p53 gene appears to target and destroy resistant and metastatic cancer cells. She has also achieved long-term cures in mice with head, neck and prostate cancers. Preliminary results in mice with breast, pancreatic and brain cancers also show promise.

Future Research Goals

Dr. Chang's future research efforts are directed toward testing ways to deliver the therapeutic agent that inhibits the oncogene or cancer-causing gene. One such method appears promise because it reaches both primary and metastatic cancer cells. Finally, Dr. Chang is currently exploring ways to administer the p53 gene through intravenous injection.

Impact on Cancer Prevention, Treatment, or Cure

Dr. Chang's work offers great promise to cancer patients with many hard-to-treat forms of cancer. By making resistant cancer cells more sensitive to conventional treatments, she can better fight primary tumors. By finding ways to reach metastatic sites, she can reduce recurrence of the disease. Her work may also allow physicians to lower doses of radiation and chemotherapy, which will result in fewer side effects.

In short, Dr. Chang's research offers great hope for better long-term results and improved survival rates. It may dramatically improve cancer patients' chance for a cure. And because of her emphasis on bringing treatment advances to patients' bedsides quickly, there is the hope that her methods may soon be available to patients.