Report describes first targeted therapy to produce remission of metastatic melanoma

April 17, 2008

BOSTON--In a demonstration that even some of the most hard-to-treat tumors may one day succumb to therapies aimed at molecular "weak points," researchers at Dana-Farber Cancer Institute report the first instance in which metastatic melanoma has been driven into remission by a targeted therapy.

The report, published in the April 20 issue of the Journal of Clinical Oncology, describes the case of a 79-year-old woman with melanoma tumors in several parts of her abdomen. When lab tests showed the tumor cells carried an abnormality in a gene called KIT, the patient enrolled in a clinical trial involving Gleevec (R) (Imatinib), a drug known to target that gene.

Four weeks after beginning therapy, imaging exams showed a dramatic reduction in tumor size and metabolism: two of the tumor masses had disappeared and several others had shrunken considerably. Four months later, the tumors were still in check, and today, nine months after the start of therapy, she continues to take the drug and her condition remains stable.

"This is the first proof of principle that we can find an Achilles' heel in melanoma" -- a gene critical to tumor cell growth and proliferation -- "and, by targeting that gene with a drug, cause the cell to die," says the study's lead author, Stephen Hodi, MD, of Dana-Farber. "It is especially exciting because there haven't been any effective treatments for melanoma patients with metastatic disease."

Although the report involves just one patient, it should inject new confidence in the fight against melanoma, Hodi says. Because previous research has failed to find any genetic Achilles' heels capable of shutting down melanoma cell growth, some researchers had speculated that none may exist for such cells. The discovery of one suggests there may be others.

KIT mutations are found in only a small percentage of melanomas, so Imatinib does not represent a universal treatment for the disease, Hodi explains. Recent studies have found KIT mutations in 11 percent of acral melanomas (which arise in skin without hair follicles, such as that of the palms, foot soles, and nail beds, and account for 5 percent of all melanomas), 21 percent of mucosal melanomas (which arise in the mucous membranes of some organs), and 17 percent of melanomas arising in chronically sun-damaged skin. For patients with these conditions, particularly those who carry a mutation in a particular section of the gene, Imatinib may well prove beneficial.

Imatinib's effectiveness against tumors with KIT mutations was first demonstrated in gastrointestinal stromal tumors (GISTs), a relatively rare malignancy of the digestive tract. An estimated 75-80 percent of GISTs have KIT mutations, and Imatinib has caused such tumors to stabilize or retreat in 75-90 percent of patients receiving it. In most of these patients, however, tumors eventually begin growing again as they become resistant to the drug.

The KIT mutation in the patient described in the study involved a protein-coding section of the gene where DNA was duplicated. This section, known as the "juxtamembrane domain," is the most frequent site of mutation in GIST, and is associated with a strong tumor response to Imatinib.

"Dramatic remissions in metastatic melanoma are something that, as physicians, we've rarely seen," Hodi remarks. "Confirming these results will require enrolling additional patients in clinical trials -- something we're actively working to accomplish."
-end-
The senior author of the study is David E. Fisher, MD, PhD, who participated in the research as a Dana-Farber faculty member and is now at Massachusetts General Hospital. Other co-authors include Philip Friedlander, MD, PhD, Annick D. Van den Abbeele, MD, George Demetri, MD, Suzanne Mac Rae, MPH, Andrea Kruse, and Jyothi Jagannathan, MD, of Dana-Farber; Christopher Corless, MD, PhD, and Michael Heinrich, MD, of Oregon Health & Science University; and Elsa Velazquez, MD, of Brigham and Women's Hospital.

Funding for the research was provided in part by the Ron Gelb Melanoma Research Fund at Dana-Farber.

Dana-Farber Cancer Institute (www.danafarber.org) is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.

Dana-Farber Cancer Institute

Related Melanoma Articles from Brightsurf:

Boosting treatments for metastatic melanoma
University of Cincinnati clinician-scientist Soma Sengupta, MD, PhD, says that new findings from her and Daniel Pomeranz Krummel's, PhD, team might have identified a treatment-boosting drug to enhance effectiveness of therapies for metastatic cancer and make them less toxic, giving patients a fighting chance at survival and improved quality of life.

A promising new tool in the fight against melanoma
An Edith Cowan University (ECU) study has revealed that a key blood marker of cancer could be used to select the most effective treatment for melanoma.

New targets for melanoma treatment
A collaborative study led by Monash University's Biomedicine Discovery Institute and the Olivia Newton-John Cancer Research Institute (ONJCRI) has uncovered new markers (HLA-associated peptides) that are uniquely present on melanoma tumours and could pave the way for therapeutic vaccines to be developed in the fight against melanoma.

Innovative smartphone-camera adaptation images melanoma and non-melanoma
An article published in the Journal of Biomedical Optics (JBO), ''Point-of-care, multispectral, smartphone-based dermascopes for dermal lesion screening and erythema monitoring,'' shows that standard smartphone technology can be adapted to image skin lesions, providing a low-cost, accessible medical diagnostic tool for skin cancer.

Antihistamines may help patients with malignant melanoma
Can a very common allergy medicine improve survival among patients suffering from the serious skin cancer, malignant melanoma?

Blood test for deadly eye melanoma
A simple blood test could soon become the latest monitoring tool for the early detection of melanoma in the eye.

Analysis of melanoma in US by age groups
This study used registry data to determine annual rates of melanoma in pediatric, adolescent, young adult and adult age groups, and the findings suggest an apparent decrease among adolescent and young adults between 2006 and 2015 but increases in older adults.

Vitamin D dials down the aggression in melanoma cells
Vitamin D influences the behaviour of melanoma cells in the lab by making them less aggressive, Cancer Research UK scientists have found.

B cells linked to immunotherapy for melanoma
Immunotherapy uses our body's own immune system to fight cancer.

Five things to know about melanoma
'Five things to know about ... melanoma' in CMAJ (Canadian Medical Association Journal) provides a brief overview of this malignant skin cancer for physicians and patients.

Read More: Melanoma News and Melanoma Current Events
Brightsurf.com 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 Amazon.com.