Melanoma: News you can Use

Melanoma: News you can Use
Lynn Schuchter, MD
Professor of Medicine
Chief, Division of Hematology/Oncology
Leader: Melanoma Program

Case of Melanosis by Isaac Parrish, MD
Rachel York, a widow aged 43 years, of dark
complexion and slender frame applied for admission
into Will’s Hospital, January 7, 1837, in consequence
of a fungous tumor on the ball of the great toe. She
stated that the tumor had been evident for the last
three years. In the spot from which it originated, there
had always been a purple mark or mole about the size
of a mulberry, which was suppose to have been
congenital. On her admission the tumor was about
half the size of a pigeons egg. Under these
circumstances, she was admitted with a view of trying
the effect of rest, position, etc., and amputating the toe
if they had no effect.

She was directed to keep the limb elevated, and to apply
mucilage of slippery elm, and a poultice of the ground
elm at night and was kept upon a light nutritious diet.
In a few days there was a slight amendment in the
appearance of the toe, which continued, however, but
for a short period. Purgatives were directed with
leeches to the groin, but she still had fever, loss of
appetite; her strength was failing, and she was rapidly
emaciating. She continued to grow worse and died on
the 21 st of March, 1837.

Microstaging of melanoma
Thickness
Clark Level
IL-2
Approved
For metastatic
melanoma
Clinical
Trials with
Raf kinase
Inhibitors
1837 1969 1975 1984 1995 2002 2009
“No remedy is
known
for melanosis”
DTIC chemo
Approved
For Stage IV
Melanoma
Major advances in staging
in surgical management
of melanoma-Less is More
High
Dose IFN
Approved
For Stage
II/III
Melanoma
B-raf mutation
Age of
targeted
Therapy for
melanoma

New: Who is at risk for melanoma
• Alarming increase in
young women
• This month in UK
melanoma most common
cancer in women 20-29
• Possible link with tanning
salons
• Increasing incidence of
melanoma in older menmost
common site trunk

News: Melanoma Prevention
• Recent study of melanoma survivors: practice
of self skin exam and sun protection the same
as the general public
• 10% of patients with melanoma at risk for
second new melanoma and increased risk for
non-melanoma skin cancer
• What about drugs: not there yet

Skin Cancer
Squamous cell
Skin cancer
Basal Cell
Skin Cancer
Melanoma

News: Vitamin D and the Sun
Mixed messages
• Vitamin D essential
for healthy bones
• New studies show
that Vitamin D may
reduce colon cancer
and breast cancer
• Possible role in
heart disease and
other medical
conditions

News: Adjuvant Therapy
Stage III Melanoma
Interferon
• One year
• One month
• 5 years
• IFN vs Pegylated IFN
Vaccine Clinical Trials
Anti-CTLA 4 antibody

News: Targeted Therapy for
Melanoma
• Targeting BRAF, c-
kit, PI3 kinase
• Selection of
patients is key

News: Distinct genetic alterations in melanoma
Superficial
Spreading
Melanoma
Abnormal gene:
B-RAF
Acral Lentiginous
Melanoma and
Mucosal
Abnormal Gene:
C-kit
Lentigo Maligna
Melanoma
Abnormal gene:
C-kit

Growth Factor
Genes broken (mutated) in a melanoma cell
C-kit
Gleevac
PI3K
PTEN
AKT
mTOR
CCI-779
Temsirolimus
RAS
N-RAS*
P16
B-Raf*
MEK
ERK
ELK
Sorafenib
Plexicon
CHR 265
Cdk4
X
Cell growth
X
BCL2
Genasense
Cyclin D

Tumor 1
Tumor 2
Tumor 3
Molecular Alteration Treatment
BRAF V600E
+ Loss of PTEN
+ MITF amplified
or mutated
BRAF/N-Ras wt
Cyclin D1 and
CDK4 overexpress
Or C-kit mutated or
over expressed
BRAF inhibitor
Sorafenib
C-Kit inhibitor
Imatinib (Gleevec)
BRAF V600E
Cyc D1 overexpress
CDK4 inhibitor
Kerian Smalley

Pretreatment Post treatment

Genetic Profiling of Tumors
• Can distinguish different subtypes of
melanoma
• Goal: to guide the selection of treatment
• Increasingly important for enrollment onto
clinical trials
• Not standard of care yet to have tumor
genotyped-consider research test

New targeted drug trials
Drug Target Trial Status
Imatinib C-KIT / PDGFRs Phase II trials Completed
Sorafenib C-Raf / B-Raf / PDGFRs /
VEGFRs
Temsirolimus
mTOR (mammalian target of
rapamycin)
Phase II trial Completed
Phase II trial Completed
Bcl-2 antisense Bcl-2 Phase III trials (with
dacarbazine) Completed
Raf-265 Braf Phase I/II trials ongoing
Sorafenib +
Temsirolimus
Proteosome
Phase III trial ongoing
Plexicon Braf Phase I trial nearing
completion, phase II to open
Dasatinib C-KIT Phase I/II trial Ongoing

Clinical trials for melanoma
• Always a good idea to consider a clinical
trial
• Availability of new agents: new targeted
therapy, immunotherapy, anti-angiogenesis
• Clinical trial does not mean placebo or that
your insurance will not pay for treatment

IL-2
Approved
For metastatic
melanoma
Clinical
Trials with
Raf kinase
Inhibitors
1800 2010
1970
2002
1860
Samuel Cooper
“No remedy is known
for melanosis”
DTIC
Approved
For Stage IV
Melanoma
BRAF mutation
Improvement in
survival for patients
with metastatic
melanoma

55 th Anniversary
Roger Bannister breaking 4 minute mile
3:59.4