Περίληψη:
The anti-epidermal growth factor receptor antibody cetuximab (Erbitux,
CTX) is currently used for the treatment of locally advanced squamous
cell carcinoma of the head and neck (LA-SCCHN), as yet with modest
effectiveness, prompting for the identification of response predictors
to this treatment and for the targeting of additional pathways
implicated in this disease. Within this scope, we investigated the
effect of SRC/STAT pathway components on LA-SCCHN patient outcome. SRC,
STAT1, STAT3, STAT5A, STAT5B, ANXA1, CAV1, IGFBP2, EPHA2, EPHB2, and MSN
relative gene expression, as well as Stat protein activation, were
assessed on LA-SCCHN tumor tissues from 35 patients treated with
combined radiotherapy (RT) and CTX-based regimens. Stat1, Stat3, and
Stat5 proteins were usually found activated in neoplastic nuclei
(70.4%, 85.7%, and 70.8%, respectively). Activated Stat3 and Stat5
were associated with each other (P = .017) and with a
CAV1(high)/MSNhigh/IGFBP2(low) profile. All patients with tumors
expressing high STAT5A/EPHA2 experienced a complete response on
RT-CTX-based treatments (12/15 complete responders, P < .0001) and a
longer progression-free survival (P = .024). Few tumors expressed high
ANXA1/CAV1/EPHA2 and low IGFBP2, a putative dasatinib response-related
profile, whereas high ANXA1 was associated with shorter overall survival
(P = .003). In conclusion, Stat activation is common in LA-SCCHN, where
overexpression of STAT5A and EPHA2 may predict for response to RT-CTX
treatments. The STAT5A/EPHA2 profile seems of particular interest for
validation in larger cohorts and in multiple tumor types because markers
for the positive selection of patients to benefit from CTX-containing
treatments are currently lacking.
Συγγραφείς:
Kotoula, Vassiliki
Lambaki, Sofia
Televantou, Despina and
Kalogera-Fountzila, Anna
Nikolaou, Angelos
Markou, Konstantinos
and Misailidou, Despina
Syrigos, Konstantinos N.
Fountzilas,
George
