My Malignant Melanoma

There are so many new drugs coming through that it's hard to keep up. Here's a summary of drugs and their targets (mostly simplified from Wikipedia entries). Let me know if I've missed any, I know there are lots more under these target headings which just have codes for names at present.

TARGET: BRAF

BRAF is a human gene that makes a protein called B-Raf. The B-Raf protein is involved in sending signals inside cells, which are involved in directing cell growth. In 2002, it was shown to be faulty (mutated) in human cancers. Drugs that treat cancers driven by BRAF have been developed. Two of these drugs, vemurafenib and dabrafenib are approved by the US FDA for treatment of late-stage melanoma.

Dabrafenib /Tafinlar

Dabrafenib acts as an inhibitor of B-Raf. Dabrafenib has clinical activity with a manageable safety profile in clinical trials of phase 1 and 2 in patients with BRAF(V600)-mutated metastatic melanoma. It was approved for use against melanoma by the FDA in May 30th, 2013.

Vemurafenib / Zelboraf

is a B-Raf enzyme inhibitor developed for the treatment of late-stage melanoma. Vemurafenib received FDA approval for the treatment of late-stage melanoma on August 17, 2011, Health Canada approval on February 15, 2012 and on February 20, 2012, the European Commission approved vemurafenib as a monotherapy for the treatment of adult patients with BRAF V600 mutation positive unresectable or metastatic melanoma, the most aggressive form of skin cancer.

LGX818

A drug by Novartis disclosed at the spring 2013 American Chemical Society meeting in New Orleans to treat melanoma with a V600E mutation in the B-RAF kinase which it inhibits. The drug is currently undergoing Phase II trials.

TARGET: MEK

A MEK inhibitor is a chemical or drug that inhibits a biochemical switch upstream of the gene which produces B-Raf, which is often overactive in BRAF-mutated melanoma. Hence MEK inhibitors can both work as standalone drugs, and increase the effectiveness of BRAF drugs.

Trametinib /Mekinist

is a MEK inhibitor drug with anti-cancer activity. It inhibits MEK1 and MEK2. In May 2013, trametinib was approved by the FDA for the treatment of melanoma.

TARGET:CTLA-4

Cytotoxic T lymphocytes (CTLs) can recognize and destroy cancer cells. However, there is also an inhibitory mechanism via a gene called CTLA-4 that interrupts this destruction. CTLA-4 inhibitors turn off this mechanism and allows CTLs to continue to destroy cancer cells.

Ipilimumab /Yervoy

Ipilimumab was approved by the FDA in March 2011 to treat patients with late-stage melanoma that has spread or cannot be removed by surgery. On February 1, 2012, Health Canada approved ipilimumab for "treatment of unresectable or metastatic melanoma in patients who have failed or do not tolerate other systemic therapy for advanced disease." Additionally Ipilimumab was approved in both the UK and European Union (EU), for second line treatment of metastatic melanoma, November 2012.

Zanolimumab/ HuMax-CD4

Action as ipilimumab. The drug is currently undergoing Phase II trials.

TARGET: PD-1

Researchers have shown that several tumour types are able to hide in plain sight by establishing a "molecular camouflage" that deceives the body's immune system into thinking they are normal and therefore allow them to grow unchecked. By utilizing the PD-1 pathway, a tumour cell can prevent the activation of T-cells and therefore may block a key step that triggers the immune system. Drugs targeting this pathway can remove the cells "camouflage", allowing the body to destroy them.

Lambrolizumab / MK-3475

is an antibody drug in development by Merck that targets the PD-1 receptor. The drug is intended for use in treating metastatic melanoma. Lambrolizumab is being studied in multiple cancer types including melanoma.

Nivolumab

Nivolumab is  an antibody drug which acts on the PD1 receptor. A Phase 1 clinical trial tested nivolumab at doses ranging from 0.1 to 10.0 mg per kilogram of body weight, every 2 weeks. Response was assessed after each 8-week treatment cycle, and were evaluable for 236 of 296 patients. Study authors concluded that:"Anti-PD-1 antibody produced objective responses in approximately one in four to one in five patients with non–small-cell lung cancer, melanoma, or renal-cell cancer; the adverse-event profile does not appear to preclude its use." Phase III clinical trials of nivolumab are recruiting in the US and EU.

TARGET: Other
 
Allovectin-7

is an immune booster. In 1999, FDA granted Allovectin-7 orphan drug designation for the treatment of invasive and metastatic melanoma.

Talimogene laherparepvec/ T-VEC

Talimogene laherparepvec, often simply called "T-VEC" is a cancer-killing (oncolytic) virus currently being studied for the treatment of melanoma and other advanced cancers. The drug was initially developed by BioVex, Inc. under the name OncoVEX GM-CSF until it was acquired by Amgen in 2011. With the announcement of positive results in March 2013, T-VEC is the first oncolytic virus to be proven effective in a Phase III clinical trial

I have updated my pages on experimental and established drugs to reflect the new possibilities. It hasn't been necessary to update my alternative medicine page - it still doesn't work.