Skin Cancer & Melanoma

Hepatic metastases remain a lethal and recalcitrant problem in the management of malignant disease, and the review by Drs. Zani and Clary of the role of hepatic metastasectomy for patients with stage IV melanoma or breast cancer is timely and welcome.

Flax, an annual plant believed to have originated in Egypt, is cultivated around internationally and is among the world’s oldest crops.

This review summarizes the existing literature that addresses the topic of metastasectomy in patients with melanoma and breast cancer.

With positive read-outs from trials over the last two years and approval of two new agents for the disease, Yervoy and Zelboraf, the field is already looking to new agents and combination trials to improve patient outcomes and survival.

Researchers have shown that the use of β-adrenoceptor antagonists (β-blockers) for 1 year or more is associated with a decreased risk of progression of thick malignant melanoma.

Researchers have identified a novel rare, germline mutation linked to a predisposition for both melanoma and renal cell carcinoma (RCC) that results in a five-fold increased risk of developing melanoma, RCC, or both.

Vemurafenib is a protein kinase inhibitor that blocks the mutated gene protein BRAFV600E so that the cascade of messages that drive cell division and prevent apoptosis is stopped, resulting in tumor shrinkage.

Highlights of the late-breaking data presentations in advanced melanoma and colorectal cancer from the European Multidisciplinary Congress held in Stockholm, Sweden, September 23-27, 2011.

Researchers have discovered that individuals carrying a mutation in the BAP1 gene are at greater risk of developing mesothelioma and uveal melanoma.

The U.S. Food and Drug Administration approved vemurafenib (Zelboraf) for the treatment of metastatic or unresectable melanoma. The new drug, also known as PLX4032, specifically targets patients whose tumors express the BRAF V600E gene mutation.

Dr. Antoni Ribas, UCLA’s Jonsson Comprehensive Cancer Center and a presenter at this year’s annual meeting of the American Society of Clinical Oncology, discusses the impact of 2 new drugs- ipilimumab (Yervoy) and vemurafenib (Zelboraf)-for the treatment of metastatic melanoma.

Using in vitro techniques and mouse models, scientists at the University of Chicago Department of Medicine and colleagues have demonstrated that downregulation of PTEN in epidermal keratinocytes predisposes skin to ultraviolet B (UVB)-induced tumorigenesis.

Ipilimumab blocks cytotoxic T-lymphocyte antigen 4 (CTLA-4) and theoretically enables cytotoxic T cells to more effectively attack melanoma cells.

Metastatic melanoma maintains a growing presence around the world, and a steady disregard for treatment efforts. But two novel drugs presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, on Sunday, suggest that medicine might finally be ready to fight back against the deadliest form of skin cancer.

It will likely not come as a surprise to anyone that the cost of cancer care is on the rise, from $104 bn in 2006 to over $173 bn in 2020. The rise in cost is driven by both the increasing cost in therapy (witness the newly approved metastatic melanoma treatment that is $120,000 for a 12-week course of therapy) and the extent of care.

For the second year in a row, metastatic melanoma (MM) research will be presented at the plenary session of the American Society of Clinical Oncology (ASCO) Annual meeting.

My 2002 article provided an overview of the various interleukin-2 (IL-2)–based treatment regimens that had been explored over the preceding two decades

Scientists at UCLA’s Jonsson Comprehensive Cancer Center and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research have identified that squamous cell carcinomas can originate from hair follicle stem cells.

A blood test could soon be used to predict the risk of the spread of cancer among melanoma patients. The study identifying the potential test was published online on April 12th in Clinical Cancer Research, and AACR journal.

The US Food and Drug Administration (FDA) on March 25 approved ipilimumab (Yervoy, Bristol-Myers Squibb) as immunotherapy for patients with late-stage melanoma, based studies showing it improved survival outcomes in these difficult-to-treat patients.

For the first time, a series of metastatic melanoma (MM) patients have been genetically tested for the constitutively activating BRAF mutation and assessed for its prognostic significance as is routinely done for breast cancer (HER2) and chronic myeloid leukemia (ABL).

Patients with advanced melanoma now have access to the BRAF inhibitor PLX4032, which has shown survival advantages in a Phase III trial, as long as they have the "right" mutation. The drug's history so far is proving a case study on the challenges of developing personalized cancer treatment.

Researchers at the NCI reported today in Nature that interferon-gamma, a protein that had been thought to contribute to an innate defense system against cancer, may in some circumstances promote melanoma and incite the development of tumors.

The experimental injectible drug PV-10 turned in positive results in a phase II study in metastatic melanoma, according to Provectus Pharmaceuticals. An objective response (OR) was observed in 49% of the 80 subjects, with 71% of subjects achieving locoregional disease control in their injected lesions. A mean progression-free survival of 11.7 months was observed among subjects achieving an OR.

Each year, nearly 60,000 new cases of melanoma are reported in the United States. The vast majority of these are cured by surgery. However, 8,000 of these patients are found to have metastatic melanoma beyond the scope of surgical cure-and this number closely approximates the annual number of deaths from this disease. This statistic illustrates the lack of progress that had been made in the treatment of advanced melanoma over the last several decades.

Currently there are only three FDA-approved drugs available for the treatment of metastatic melanoma: dacarbazine, interleukin-2, and the lesser-used hydroxyurea. None of these drugs has been shown to improve overall survival (OS). The review by Thumar and Kluger provides a well-balanced overview of ipilimumab, the first agent to demonstrate a survival benefit in patients with metastatic melanoma.[1] The response to ipilimumab is most notable for its durability, a feature rarely observed in patients with high tumor burden or in response to other systemic therapies. However, a minority of patients (10% to 15%) treated with ipilimumab meet standard criteria for radiographic response. In this commentary, we focus on the question of how we can build on the success of ipilimumab. We briefly review one area of active investigation: the combination of ipilimumab with targeted inhibitors of BRAF.

Antibody-based targeting of the immune suppressor molecule cytotoxic T-lymphocyte antigen 4 (CTLA-4) with ipilimumab has been studied in metastatic melanoma in a number of clinical trials, including a recent phase III trial. This marks the first randomized clinical trial reporting an overall survival benefit using immune modulation in metastatic melanoma. Along with its therapeutic benefits, ipilimumab presents unique challenges to clinicians; these are related to the monitoring of treatment response and the management of drug-related toxicities. This drug is currently being investigated in various cancers, and its indications are likely to be expanded.

The authors provide a timely and relevant review of the role that the immune system plays in regulating tumor growth and how immune modulation can alter tumor response. This review follows from the recently published phase III trial of ipilimumab,[1] a monoclonal antibody to cytotoxic T-lymphocyte antigen 4 (CTLA-4) and the first therapy in several decades to produce prolonged overall survival (OS) in patients with metastatic melanoma. While this outcome underscores the importance of this therapy in treating metastatic melanoma, its clinical applicability, at least on a widespread level, necessitates further exploration.

Two cousins with cancer were randomized to different arms of a clinical trial of Roche’s melanoma drug, PLX4032. The implications were covered in a NYTs story, which questioned the ethical implications of our current trial design.

Ipilimumab has received FDA priority review status, according to Bristol-Myers Squibb. The review will focus on use of the drug in adult patients with previously treated advanced melanoma.