‘Reading’ Cancer Cells : City of Hope Researcher’s Work Detects Patient’s Drug Resistance

Charts mounted on the walls of the small bungalow housing a cancer research unit at the City of Hope in Duarte illustrate the results of a job well done.

Although the setting is unassuming, the importance of the experiments is etched in the smile of the proud scientist who tends to the flow sheets and oversees the successful work that the graphs portray.

Dr. Kevin Scanlon has found a way to “read” the genetic blueprints of cancer cells, the very messages that tell such cells what to do and how to do it--especially how to become resistant to the killing power of chemotherapeutic drugs.

Scanlon’s new gene-reading technique amounts to an early-detection test for drug resistance in patients apparently losing their fight against cancer because their malignant cells have neutralized the effects of cancer-destroying drugs.

The mechanisms that create such resistance and allow cancer genes to crank out malignant cells by the deadly millions have stumped many a brilliant mind. But in Scanlon’s lab, the bar graphs and flow sheets on the walls tell a simple story belying the complexity of their science.

They show how a newly designed test can decipher molecular messages inside cancer cells and may revolutionize the use of chemotherapy while helping to save the lives of cancer victims worldwide.

Well-Known Dogma

Scanlon has successfully poked his way into the genetic activities of living malignant cells, basing his work, in part, on one of the well-known dogmas of molecular biology: RNA to DNA to protein.

DNA, deoxyribonucleic acid, contains the genetic information in all cells. When a cell is replicated, a genetic messenger, RNA or ribonucleic acid, copies that information to create a new double-helical, DNA molecule.

The DNA, which contains the genetic blueprint for life, in turn, codes for proteins.

In the new test, scientists monitor certain cancer-associated enzymes, proteins that can make a cell resistant to chemotherapeutic drugs by detecting levels of messenger RNA, genetic material involved in the cell’s functions.

By pinpointing the genetic material responsible for making those enzymes, the test can alert doctors to the growing drug resistance of cancerous cells early in the development of a patient’s disease.

“If there’s an increase in messenger RNA, then you have confirmation that the tumor cells are resistant,” explained Scanlon, who heads the City of Hope National Medical Center’s section of biochemical pharmacology.

Scanlon’s team tested cell resistance in samples of leukemia, ovarian, breast and colon cancer.

What makes this test an important advance in cancer research, he says, is that it can detect resistance to chemotherapy in just a few hundred cells extracted from cancerous tissue.

Currently, drug resistance is determined by either a CAT scan or X-ray which can show that a tumor has changed dramatically in size. A tumor that grows despite administration of chemotherapeutic drugs often spreads by way of cells that have become resistant to such attack.

However, by the time doctors are able to detect that growth, and thus cancer cell resistance, it is often too late to switch to a new chemotherapeutic drug to which the cells are not immune.

“You have to have over 1 billion cells of tumor before a CAT scan can detect resistance,” Scanlon said.

Tumor cells, unfortunately, are equipped with genes that not only make them immortal under certain conditions but also permit them to outwit doctors who attempt to kill them with some of the most powerful anti-cancer agents known.

As part of the study, Scanlon and his colleagues tested cancer cells with cisplatin and 5-fluorouracil, two widely used chemotherapeutic drugs. They found that although malignant cells are initially killed, many gradually develop resistance to treatment.

That resistance apparently is imparted by certain enzymes that become more active in the presence of the two cancer-fighting drugs. These enzymes also increase their activity to counter the drugs, rendering a patient defenseless against the spread of cancer.

But with the new technique--a chemical assay--a small sample of cancerous tissue can reveal the level of RNA present, letting doctors know within a matter of hours if the cancer cells are fighting off the drug.

With conventional techniques, confirmation of resistance may take up to a month, even years in some cases, Scanlon said.

Refining Technique

“We can use this assay to confirm what we have determined by conventional methods, but using a thousand times less tissue,” he said.

Although his test for cancer drug resistance is not yet available publicly, Scanlon said he is working on refining the technique.

Scanlon recently discussed the new test at the American Assn. for Cancer Research’s meeting in New Orleans.

“It was just 35 years ago,” he said, “when we first learned the structure of the DNA molecule and in those 35 years we’ve made a quantum leap in understanding the molecular biology of the cancer cell.

“We’re just now starting to find out what the good genes are and what the bad genes are and the mechanisms of how they regulate the cell.”