June 1 Clinical Cancer Research Highlights

The lymph node basin is the most frequent site of melanoma metastasis, and detecting micrometastasis in melanoma-draining lymph nodes such as the sentinel lymph node is important for staging and prognosis. In this study, Goto and colleagues detected micrometastasis by performing immunohistochemistry with monoclonal antibodies against cell surface high molecular weight-melanoma-associated antigen (HMW-MAA). Their analysis demonstrated that anti-HMW-MAA immuno­histochemistry significantly improves detection of micrometastasis in lymph nodes, compared to conventional immunohistochemical approaches with anti-MART-1 and HMB-45 antibodies. The HMW-WAA biomarker assay provides both better specificity and sensitivity for detecting melanoma micrometastasis. 

 

Chemotherapy is an integral part of the treatment strategy for women with hormone-insensitive breast cancer. However, there is a need to identify markers that can be used to predict or monitor the efficacy of chemotherapy. In this study, Fiegl and colleagues analyzed DNA methylation in pre-treatment core biopsies, and in pre- and post-chemotherapy serum samples from breast cancer patients using MethyLight (a sensitive fluorescence-based real-time PCR technique). They found that NEUROD1 DNA methylation is a chemosensitivity marker in estrogen receptor negative breast cancer and, as such, could potentially be used as a tool for predicting response to chemotherapy.

The α-emitting nuclide Actinium-225 is a promising isotope for targeted cancer therapy. In this study, Miederer and colleagues studied the potency and toxicity of Actinium-225 conjugated to a somatostatin analogue (²²⁵Ac-DOTATOC) for treating neuroendocrine tumors. Despite evident renal toxicity at high doses, they were able to identify a therapeutic window at low doses using a xenograft mouse disease model. Further, the therapeutic potency of ²²⁵Ac-DOTATOC compared favourably to that of the β-emitting radio-peptide conjugate Lutetium-177-DOTATOC. This study provides a proof of concept that peptides may be suitable carrier molecules for α-particle emitting isotopes in neuroendocrine tumor treatment.