Evaluation of Pathway Modulation by Raf, MEK, & Kinase Inhibitors

The study will evaluate the modulatory effect of systemic Raf inhibition in the MEK/ERK and
PI3 /Akt/mTOR pathways in patients undergoing targeted therapy for metastatic disease.

Changes in relevant proteins will be evaluated using a combined protein expression
methodology that in includes immunohistochemistry (IHC) and reverse phase protein microarray
(RPPA) technology.

The primary endpoint of this study will be assessed in normal skin and skin acutely exposed
to solar simulated light

Inclusion Criteria:

- Subjects who have not yet initiated but plan to undergo dosing with a Tyrosine Kinase
inhibitor (TKI) or Raf inhibitor, either alone or with a MEK inhibitor, for treatment
of metastatic melanoma, colon cancer, hepatic cell carcinoma, or thyroid cancer.

- Individuals with normal skin and Fitzpatrick skin type II, III or IV.

- Individuals who are willing to limit sun exposure to the body during the study period,
and who agree to wear protective clothing and SPF 50 broad spectrum sunscreen or
sunblock on exposed skin when they are outdoors.

- Individuals who have the ability to understand and willingness to sign an informed
consent before initiation of study procedures, after the nature of the study is
explained to them and they have asked any questions.

- Individuals with a Karnofsky Performance Status of at least 80%.

Exclusion Criteria:

- Individuals with any inflammation or irritation of the skin at the test area
(buttocks), or any skin conditions felt by the study physician to contraindicate
enrollment.

- Individuals with a history of any skin cancer, melanocytic lesions, actinic keratoses
or actinic damage in the test area are ineligible. History of such conditions at a
body site other than the test area is not exclusionary if in the opinion of the study
physician it will not pose a risk to the subject.

- Individuals who are immunosuppressed by virtue of medication or disease, as determined
by the examining study physician. This includes AIDS patients and subjects taking oral
steroids.

- Individuals with active infection, psychiatric illness, or other situations that in
the opinion of the study physician limit compliance or interfere with the study
regimen.

- Individuals with a history of photosensitive diseases including, but not limited to,
Lupus Erythematosus, pseudoporphyria, or other diseases that in the opinion of the
study physician would pose a risk to the subject or interfere with the study.

- Individuals who have used photosensitizing drugs within the last 30 days prior to
study enrollment, or who will be using a photosensitizing drug during the time of the
study.

- Individuals who have used any topical medication other than emollients on the test
area within 30 days prior to study enrollment.

- Individuals who have used retinoids, steroids, 5-fluorouracil, Levulan, Vaniqua
(eflornithine), Solaraze, or Imiquimod (Aldara®) anywhere on the body within 30 days
prior to enrollment.

- Individuals must not take mega-doses of vitamins. Mega-doses are defined as more than
5 capsules of standard multivitamins daily or more than the Tolerable Upper Intake
Levels of Vitamins, as defined by the Institute of Medicine, National Academy of
Sciences. Such vitamin therapy must be discontinued at least 30 days prior to study
entry.

- Individuals with a history of natural or artificial sun exposure to the buttocks
within 30 days of study participation.

- Individuals with Fitzpatrick skin type I

- Individuals with Fitzpatrick skin type V or VI

- Individuals enrolled in or who plan to enroll in a clinical intervention trial. There
must be a 30-day period between completing a previous study and enrolling in this
study. The Principal Investigator will have the option to consider an exception for
patients on drugs of interest for the purpose of this study.

- Individuals with a known allergy to lidocaine.