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.
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| STAGE 0 |
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.
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| STAGE II |
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.
 |
| STAGE IV |
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.
