Sumanta Kumar Pal | PubMed Health

PubMed2006

Targeting HER2 Epitopes.

Variable expression of the HER2 receptor has been implicated in the pathogenesis of a number of malignancies. Many therapeutic modalities have been devised that target the receptor and downstream molecular pathways. The humanized monoclonal antibodies trastuzumab and pertuzumab bind epitopes on the extracellular domain, resulting in cell growth inhibition though a number of proposed mechanisms. Peptidomimetic agents represent short amino acid sequences containing structural features of the antibody complementarity determining regions (CDRs), and appear to have similar inhibitory properties in experimental models. RNA aptamers are ribonucleotide sequences that also exhibit complementarity with extracellular epitopes and lead to growth inhibition. Recent data suggest a synergistic interaction of HER2 epitope-targeting agents when used in combination.

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PubMed2005

Epidermal growth factor receptor and signal transduction: potential targets for anti-cancer therapy.

Agents targeting the epidermal growth factor receptor (EGFR) pathway hold particular promise for the treatment of patients with advanced disease, for whom standard chemotherapy is generally palliative. Expression of EGFR on numerous types of solid tumors, and the association of EGFR activation with tumorigenic processes including proliferation, anti-apoptosis and metastatic spread, make this pathway a particularly compelling target for rational drug design. The two classes of anti-EGFR agents in late-stage clinical testing include antibodies directed toward the extracellular EGFR domain (cetuximab, panitumumab) and small molecule tyrosine kinase inhibitors (gefitinib, erlotinib), which inactivate the receptor enzyme activity. However, important issues remain to be addressed. These include the development of appropriate predictive markers for response, such as improved tests for EGFR activity, correlation of rash with response and potential pharmacogenomic approaches; the sequencing and combination of these agents with chemotherapy and irradiation; and the possible role of these agents in the treatment of patients with earlier stage disease.

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