Precision Cancer Medicine

for Colon Cancer

Precision Cancer Medicine & Personalized Colon Cancer Care

There is no longer a “one-size-fits-all” approach to cancer treatment. Even among patients with the same type of cancer, the behavior of the cancer and its response to treatment can vary widely. By exploring the reasons for this variation, researchers have begun to pave the way for more personalized cancer treatment. It is becoming increasingly clear that specific characteristics of cancer cells and cancer patients can have a profound impact on prognosis and treatment outcome. Although factoring these characteristics into treatment decisions makes cancer care more complex, it also offers the promise of improved outcomes.

The idea of matching a particular treatment to a particular patient is not a new one. It has long been recognized, for example, that hormonal therapy for breast cancer is most likely to be effective when the breast cancer contains receptors for estrogen and/or progesterone. Testing for these receptors is part of the standard clinical work-up of breast cancer. What is new, however, is the pace at which researchers are identifying new tumor markers, new tests, and new and more targeted drugs that individualize cancer treatment. The purpose of precision cancer medicine is not to categorize or classify cancers solely by site of origin, but to define the genomic alterations in the cancers DNA that are driving that specific cancer.

Precision cancer medicine utilizes molecular diagnostic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. Once a genetic abnormality is identified, a specific targeted therapy can be designed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells. Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack the cancer cells with specific abnormalities, leaving normal cells largely unharmed.

By testing an individual’s colon cancer for specific unique biomarkers doctors can offer the most personalized treatment approach utilizing precision medicines.

Colorectal Cancer Biomarkers

Genetic Mutations

  • The RAS Genes: KRAS and NRAS: KRAS and NRAS genes play an important role i1 If cancer has a KRAS or NRAS mutation drugs that target EGFR; erbitux® (cetuximab)2 and vectibix® (panitumumab).3 may not work effectively. “Wild type” means you do not have the mutation and the drugs may provide some benefit. All patients with advanced colon cancer should undergo RAS biomarker testing before beginning treatment.
  • BRAF: BRAF is also a gene that signals cells to divide. Patients with mutant BRAF genes generally have a poorer prognosis (chance of survival and worse side effects) but may benefit from treatment with a precision cancer medicine.
  • PIK3CA: While somewhat new, a growing number of clinicians are testing for mutant PIK3CA genes; particularly in patients who have early-stage colorectal cancer. There is some suggestion that aspirin use may help decrease the risk of recurrent colorectal cancer in patients with early stage disease and PIK3CA mutation.
  • Microsatellite Instability High (MSI-H) MSI-H is a DNA abnormality found in about 15% of colon cancers. It is most often found in tumors associated with genetic syndromes like Lynch syndrome but can also occur sporadically. MSI-H is what “happens” when the genes that regulate DNA function don’t work correctly. These DNA regulating genes, known as Mismatch Repair Genes (MMR), work like genetic “spell checkers.” When problems occur in these spell-checking MMR genes, it means that areas of DNA start to become unstable. A high frequency of instability is called MSI-H. Patients with MSI-H tumors may respond differently to certain treatment. It is important to test colon cancers for this trait because it can help determine if the colorectal cancer is related to an inherited family syndrome.

Carcinoembryonic Antigen (CEA) CEA is a protein that may be higher in colorectal cancer patients. High levels of CEA may indicate that cancer is present or a treatment is not working. Low levels may indicate that the body is responding to a treatment.

OncoType DX: Is a test that may help guide treatment decisions for patients with Stage II colon cancer. This test estimates the risk of cancer recurrence by evaluating the activity of certain genes in a sample of tumor tissue.4 Risk of recurrence can vary greatly among patients with Stage II colon cancer, and adjuvant (post-surgery) therapy is not routinely recommended for all patients with Stage II colon cancer, but may be considered for high-risk patients.

Treatment information concerning colon cancer is categorized and discussed by the stage and presence or absence of specific biomarkers. In order to learn more about the most recent information available concerning the treatment of colon cancer, select the appropriate stage.

Learn more here: http://oncoprecision.org/

References


1 Kuhry E, Schwenk WF, Gaupset R, Romild U, Bonjer HJ. Kuhry E, Schwenk WF, Gaupset R, Romild U, Bonjer HJ. Cochrane Long-term results of laparoscopic colorectal cancer resection. Cochrane Database of Systematic Reviews 2008;2:CD003432. Cochrane Database of Systematic Reviews 2008;2:CD003432.

2 Karapetis CS, Khambata-Ford S, Jonker DJ et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. New England Journal of Medicine. 2008;359:1757-65.

3 Amado RG, Wolf M, Peeters M et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. Journal of Clinical Oncology. 2008;26:1626-1634.

4 National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology.™ Colon Cancer. V.3.2008. © National Comprehensive Cancer Network, Inc. 2008. NCCN® and NATIONAL COMPREHENSIVE CANCER NETWORK® are registered trademarks of National Comprehensive Cancer Network, Inc.