Genes can determine chemotherapy program for colorectal cancer patients

May 13, 2001

Certain genes in tumors of patients with metastatic colorectal cancer can predict whether further chemotherapy will help prolong their lives

SAN FRANCISCO, May 14, 2001--Testing the tumors of advanced colorectal cancer patients can determine whether patients who have already failed a round or more of chemotherapy would benefit from further chemotherapy, according to a study by USC/Norris Comprehensive Cancer Center oncologists presented this weekend at the American Society of Clinical Oncology annual meeting.

The researchers showed that when given a combination of two chemotherapy drugs--5-FU (fluorouracil) and oxaliplatin--patients whose tumor cells expressed low levels of two key enzymes survived five times longer than patients whose tumor cells expressed high levels of the enzymes.

According to research oncologist Heinz-Josef Lenz, M.D., associate professor of medicine at the Keck School of Medicine of the University of Southern California, the study is the first to look at the use of such tumor testing and clinical outcome with the drug oxaliplatin.

The research is part of USC/Norris oncologists' ongoing efforts to customize the most effective and tolerable treatments for each colorectal cancer patient based on the patient's genes and the unique characteristics of the cancer.

Lenz and colleagues conducted the clinical study of 50 patients with advanced colorectal cancer. Patients had already failed at least one prior chemotherapy regimen before the oncologists placed them on 5-FU and oxaliplatin.

Meanwhile, researchers tested patients' tumor biopsies to see how much of two key enzymes they expressed--an amount that varies from patient to patient.

Two important genes give orders to express these enzymes: the excision repair cross-complementing gene 1 (ERCC1) and thymidylate synthase (TS) gene.

In a healthy person, ERCC1 helps cells repair damaged DNA, while the body uses TS to make DNA. Unfortunately, though, cancerous tumor cells use the enzymes, too. They can feed off the TS to reproduce their own DNA, and use ERCC1 to fix DNA damaged through chemotherapy.

The more the genes can give orders to make the two enzymes, the more the cancerous tumors can successfully resist certain anti-cancer drugs, Lenz explains. By using a unique technology to test tumor tissue samples, the USC/Norris researchers were able to determine the amount of TS and ERCC1 expressed by the genes in each patient's tumors.

In the USC/Norris study, the median survival time for patients with low TS gene expression was 311 days, significantly longer than the 57 days survived by the typical patient with high TS gene expression. Similarly, the median survival time for patients with low ERCC1 expression was 311 days, more than five times longer than the 57 days survived by the typical patient with high ERCC1 gene expression.

"These data strongly indicate that if considered separately, either ERCC1 or TS gene expression levels in those heavily pretreated patients with metastatic colorectal tumors predict for clinical outcome," Lenz says.

Such information could help patients and physicians make treatment decisions, including which chemotherapy drugs to administer and whether more chemotherapy is the right choice.
The USC/Norris oncologists conducted the research in cooperation with colleagues at Response Genetics Inc. The company was founded by Kathleen Danenberg, research laboratory specialist at USC/Norris, and Peter Danenberg, Ph.D., USC professor of biochemistry and molecular biology, and focuses on molecular services for oncologists and cancer patients.

Colorectal cancer is the third most common cancer in the United States, and experts expect 130,000 new cases to be diagnosed this year. The five-year survival rate for patients with advanced or metastatic disease is less than 10 percent.

University of Southern California

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to