Development of new targeted therapies for breast cancer

Abstract

Clinical application of truly targeted therapy relies on identification of a specific molecular feature (the target) that is biologically relevant, reproducibly measurable and definably correlated with clinical benefit. Ideally the target should be crucial to the tumor's malignant phenotype. The target must be easily measurable in readily obtained clinical samples. Interruption, interference or inhibition of the target should yield a clinical response in a significant proportion of patients whose tumors express the target but in few patients whose tumors do not express the target. As such, targeted therapy offers the twin hopes of maximizing efficacy while minimizing toxicity. A critical review of the hallmarks of malignancy provides a framework for considering potential targets and novel therapeutic interventions. The hallmarks of malignancy include uncontrolled proliferation, insensitivity to negative growth regulation, evasion of apoptosis, lack of senescence, invasion and metastasis, angiogenesis, and genomic elasticity. Existing therapies predominantly target proliferation either with cytotoxic agents, ionizing radiation or inhibition of estrogen receptor and HER2 growth factor signaling pathways. Further improvements in therapy must attack the other hallmarks of malignancy and will undoubtedly be accompanied by better means of individual patient selection for such therapies. Indeed, each of these hallmarks presents a therapeutic opportunity. To believe otherwise would be to assume that a feature is both biologically crucial yet therapeutically unimportant, an unlikely paradox.

Dehydrocostuslactone disrupts signal transducers and activators of transcription 3 through up-regulation of suppressor of cytokine signaling in breast cancer cells

“…Different treatment strategies have been proposed with the intention to reduce mortality rates, including surgery and radiotherapy and adjuvant chemo-or hormonotherapies (2). However, breast cancer is particularly challenging because it is highly resistant to radiation and conventional chemotherapeutic agents, and this resistance is associated with a poor prognosis for this metastatic disease, particularly in hormone receptor-positive breast cancer (1,3). About 30% to 40% of women with this form of cancer will develop metastasis and eventually die from this disease (4).…”

Predictive Potential of Angiogenic Growth Factors and Circulating Endothelial Cells in Breast Cancer Patients Receiving Metronomic Chemotherapy Plus Bevacizumab

“…Furthermore, it is not fully understood whether the benefit from the combination is similar for all patients or greater in some patients and reduced (or absent) in others. Thus, there is a compelling need for biomarkers useful for distinguishing between patients who are likely to benefit from the combination therapy from those for whom the balance between the benefit and the side effects is less convenient (1)(2)(3)(4)(5).…”

High-Throughput Screening Identifies Cardiac Glycosides as Potent Inhibitors of Human Tissue Kallikrein Expression: Implications for Cancer Therapies

“…Targeting the proteins involved in neoplastic initiation and progression seems to be one of the most promising strategies for cancer therapy (1). Thus, as a first step, identification of the key players associated with cancer progression is critical.…”