Somatostatin receptors (SSTRs), especially SSTR subtype 2, are found expressed at relatively higher levels in many
tumor cells and in tumoral blood vessels relative to normal tissues. This creates an opportunity for developing various cytotoxic SST conjugates that selectively target SSTR2-specific sites. Accordingly, some potent chemotherapeutic agents such as
camptothecin (
CPT),
methotrexate (MTX),
paclitaxel (PTX) and
doxorubicin (DOX) have been coupled to SSTR2-preferential
somatostatin (SST) analogs. These new cytotoxic SST conjugates display significant SSTR-selective anti-
tumor abilities in many different types of
tumors. For instance, the
CPT-SST conjugate
JF-10-81, in which
CPT is coupled to the N-terminus of a SSTR2-specific SST analog (JF-07-69), had wide ranging anti-
tumor and anti-angiogenic ability. This conjugate also showed an ability to overcome multi-drug resistance (MDR) in SSTR-over-expressing and
CPT-insensitive human pancreatic
carcinoid BON cells. Notably, another DOX-SST conjugate,
AN-238, made by coupling pyrrolino-DOX to the SST analog
RC-121, displayed indirect anti-
tumor activity against SSTR-negative,
non-small cell lung cancer H-157
tumor growth by directly targeting SSTR-positive tumoral vessels of host mice. These cytotoxic SST conjugates should deliver chemotherapeutic agents to receptor-specific sites, enhance anti-
tumor efficacy, reduce toxic side effects to normal tissues, and to some extent, overcome MDR. These and other
peptide conjugates may possibly represent a newer generation of receptor-targeted
cancer therapeutics. This review discusses the progress with reference to SST-based and SSTR-selective cytotoxic
cancer therapy.