NcXHF

KLIMSTRA ET AL
WD-NETs (grade 1 and 2) are relatively indolent (with a natural
history that can evolve over many years or decades),
closely resemble non-neoplastic neuroendocrine cells, and
demonstrate production of neurosecretory proteins, such as
chromogranin A and synaptophysin. Only WD-NETs arise
in patients with inherited neuroendocrine neoplasia syndromes
(e.g., MEN1). Surgery is the mainstay of therapy for
WD-NETs, which are relatively unresponsive to chemotherapy
(although several cytostatic agents have proven activity).
In contrast, PD-NECs (grade 3) are uniformly highly aggressive,
demonstrate a high proliferative rate, and are classifıed
as small cell carcinoma or LCNEC. PD-NECs typically harbor
molecular alterations distinctive from WD-NETs (leading
to loss of Rb and P53 function), and some alterations are
site-specifıc (e.g., TMPRSS2-ERG gene rearrangement in
NEPC). PD-NECs exhibit marked but transient sensitivity to
platinum-based chemotherapy and are usually metastatic at
diagnosis. Although validated biomarkers of response are
not yet available, advances in the understanding of the molecular
basis of NETs may lead to new diagnostic and therapeutic
strategies, and holds the promise of an individualized
therapy.
Disclosures of Potential Conflicts of Interest
Relationships are considered self-held and compensated unless otherwise noted. Relationships marked “L” indicate leadership positions. Relationships marked “I” are those held by an immediate
family member; those marked “B” are held by the author and an immediate family member. Institutional relationships are marked “Inst.” Relationships marked “U” are uncompensated.
Employment: None. Leadership Position: None. Stock or Other Ownership Interests: None. Honoraria: None. Consulting or Advisory Role: Emily
Bergsland, Celgene, Genentech/Roche, Lexicon, Inc., Novartis. David Klimstra, Ipsen, Wren Laboratories. Rogerio Lilenbaum, Boehringer Ingelheim, Genentech/Roche.
Speakers’ Bureau: None. Research Funding: Emily Bergsland, Genentech/Roche (Inst), Lexicon (Inst), Novartis (Inst), Sanofi (Inst). Patents,
Royalties, or Other Intellectual Property: None. Expert Testimony: None. Travel, Accommodations, Expenses: Emily Bergsland, Lexicon. Rogerio
Lilenbaum, Roche. Other Relationships: None.
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