Report describes first targeted therapy to produce remission of metastatic melanoma

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."

Source: Dana-Farber Cancer Institute

Related stories:

Patient's own infection-fighting T cells put late-stage melanoma into long-term remission
Case is first to show safety and effectiveness of using cloned cells alone to kill tumors
Researchers describe the first successful use of a human patient's cloned infection-fighting T cells as the sole therapy to put an advanced solid-tumor cancer into long-term remission. A team led by Cassian Yee, M.D., an associate member of the Clinical Research Division at Fred Hutchinson Cancer Research Center, reports these findings in the June 19 issue of the New England Journal of Medicine.
Immune molecule that plays a powerful role in avoiding organ rejection identified
When a mouse's immune system is deciding whether to reject a skin graft, one powerful member of a molecular family designed to provoke such a response can effectively reduce the visibility of the mouse's own cells and help the graft survive, researchers say.
Overcoming Drug Resistance—Nanoparticles Trigger Built-In Cell-Death Signal
One of the most vexing problems in treating cancer is the propensity of tumors to develop resistance to a wide range of anticancer drugs. Over 70 percent of ovarian cancer patients, for example, have drug-resistant tumors at the time of their initial diagnosis, and virtually all patients who relapse have drug-resistant tumors.
Combination therapy packs 1-2 punch against melanoma
Disabling a protein frequently found in melanoma tumors may make the cancer more vulnerable to chemotherapy, according to a pilot study led by researchers in the Duke Comprehensive Cancer Center.
New combination therapy safe, promising for melanoma patients
The combination of two different biotherapies may be beneficial for patients with inoperable melanoma, according to a University of Pittsburgh Cancer Institute (UPCI) study presented at the 44th annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.
Targeted therapy plus chemotherapy may pack 1-2 punch against melanoma
By targeting and disabling a protein frequently found in melanoma tumors, doctors may be able to make the cancer more vulnerable to chemotherapy, according to a new study by researchers in the Duke Comprehensive Cancer Center.
Scientists identify interacting proteins key to melanoma development, treatment
Researchers have discovered how a mole develops into melanoma by showing the interaction of two key proteins involved in 60-70 percent of tumors. The Penn State scientists also demonstrate that therapeutic targeting of these proteins is necessary for drugs to effectively treat this deadly form of cancer.
Melanoma of the rectum: A rare entity
A 41-year-old man presented with a 6-month history of changed defecation patterns and rectal bleeding. A 3-cm polypoid tumor of the lower rectum was found at rectosigmoidoscopy. Dissemination studies did not show any metastases. He underwent an abdominoperineal resection. The histopathology of the specimen showed a melanoma. Two years after the resection, metastases in the abdomen and right lung were found. He died a year and a half later.

News discussion:

Medicine & Health news