Tuesday, May 6, 2014

Malignant Melanoma Staging and Advances in Chemical Agents.

This is my first blog post regarding my cancer project with Ellie Pringle.  First things first….I wanted to learn the stages and classifications of developing malignant melanoma.  An article from the National Cancer Institute gave an overview of the stages of skin cancer and the symptoms associated with each.  A melanocyte is a melanin-producing cell that is located in the bottom layer of our skin’s epidermis.  Melanin is the primary determinant of skin color in humans and is a derivative of the amino acid tyrosine. 

            The American Joint Commission on Cancer is the most common staging system used for melanoma.  In order to properly stage melanoma, a biopsy is recommended in order to access the depth of the tumor, mitotic rate, and presence of ulcerations.  Stage 0 of melanoma consists of abnormal melanocytes in the outer layer of skin.  These mutated melanocytes hold the potential of spreading onto other parts of the skin or adjacent tissues. 
            Stage Ia is where the tumors begin to appear.  The tumor is 1mm with no ulceration.  Stage Ib consists of either a 1mm tumor with ulcerations or a 2mm tumor with no ulcerations.  In stage II, melanoma is developing into larger tumors with a higher chance of ulcerations through the out layer of the skin. 
            In stage III the thickness of the tumor is no longer measured in determining the stage of the cancer.  The cancer may have spread to one or more lymph nodes.  Very small tumors may be visible about 2cm away from the site of origin of cancer.  Stage IV is the last stage of malignant melanoma.  Cancer has spread to other places in the body (lung, liver, brain, bone, ect..) The cancer be present in places on the body quite far away from the original tumor. 
            Knowing the stages and development of melanoma have led to recent advances in drug therapies.  Recent discoveries of mutations associated with melanoma have transformed skin cancer treatment from mostly surgical procedures to targeted drug therapies.  This article from Wiley Online Library discusses this new era of targeted drug therapies associated with melanoma.
            One of the oncogenic drivers of melanoma discovered recently is mutation in BRAF.  Proteins made from the BRAF gene trigger the MAPK pathway leading too unchecked cell growth and prevention of cell death.  BRAF mutations were detected within 66% of patients with malignant melanoma.  80% of these cases experienced a single substitution of glutamic acid for valine in codon 600. 
           Knowing the biology and location of the majority of BRAF mutations has led to clinical benefits.  The first treatment showing positive results was vemurafenib.  Results of high survival benefits led to FDA approval in August 2011.  Studies regarding vemurfenib displayed 80% of patients with tumor size reduction.
            The second BRAF inhibitor to come onto the scene was dabrafenib.  Dabrafenib is an ATP-competitive inhibitor that selectively inhibits BRAF.  This agent has already shown promising results in the treatment of mutant melanoma.  The efficacies of both agents discussed seem to be similar.  Oncologists base their decision between these drugs on the side effects associated with each.  In my next blog, I will further discuss the biology of BRAF V600 mutations, the efficacy of combination therapy and the toxicity associated with these chemical agents.      

Saranga-Perry, Vita, Dr., Chenwi Anbi, Dr., Jonathon S. Zager, Dr., and Ragini Kudchadkar, Dr. "Recent Developments in the Medical and Surgical Treatment of Melanoma." - Saranga-Perry. Wiley ONline Library, 26 Mar. 2014. Web. 06 May 2014. <http://onlinelibrary.wiley.com/doi/10.3322/caac.21224/full>.

"Melanoma Treatment (PDQ®)." - National Cancer Institute. N.p., n.d. Web. 06 May 2014. <http://www.cancer.gov/cancertopics/pdq/treatment/melanoma/Patient/page2#Keypoint12>.

Menzies, Alexander. "Combination BRAF and MEK Inhibitors." Medscape. N.p., n.d. Web. 06 May 2014. <http://www.medscape.com/viewarticle/810688_2>.