Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents) - Volume 12, Issue 2, 2012

The past few decades have witnessed remarkable changes in the management of patients with cancer. Although more patients than ever before are being diagnosed with cancer, the survival rate for patients with cancer has increased substantially [1]. The refined use of surgical strategies, conventional cytotoxic agents, and radiotherapy and the development of targeted agents have been integral components of this succes Read More

In the early 1960s, inorganic pyrophosphate (PPi) was found to be present in body fluids and to act as a natural inhibitor of calcification by its interaction with hydroxyapatite. In addition to inhibiting the formation of calcium phosphate, PPi also inhibited dissolution of hydroxyapatite crystals, which made it interesting for pharmacologic applications in the treatment of diseases associated with excessive bone resorption. Howev Read More

Bone is a common site of metastasis from advanced cancers, and metastasis to bone accounts for the majority of distant recurrences from breast and prostate cancers. Bone metastases are characterized by increased rates of bone turnover. Bisphosphonates are extensively used in the treatment of metastatic bone disease to reduce the rates of osteolysis and the risk of skeletal-related events. In addition, bisphosphonat Read More

Despite progress in surgical and adjuvant therapy, a subset of patients with early stage breast cancer experience disease recurrence and/or distant metastases. Disseminated tumor cells (DTCs) in the bone marrow are believed to be the source of late relapses in bone and other tissues. Bone is the most common site of breast cancer metastasis, and agents that modify the bone microenvironment could therefore affect the disea Read More

Bisphosphonates inhibit osteoclast-mediated bone resorption and have been used extensively to prevent skeletal-related events in patients with bone lesions from multiple myeloma (MM). In addition, in vitro and in vivo preclinical data suggest that bisphosphonates also have antimyeloma properties that may induce myeloma cell apoptosis, activate an anticancer immune response, inhibit angiogenesis, and reduce tumor b Read More

Anticancer therapies have traditionally been targeted directly against cancer cell growth. However, newer treatment strategies also target the microenvironment that supports metastatic cancer cell growth. Bisphosphonates are the standard of care for maintaining bone health in patients with bone metastases from solid tumors and bone lesions from multiple myeloma, and emerging evidence supports potential anticancer Read More

Bisphosphonates are the current standard of care for patients with bone metastases from advanced solid tumors. Zoledronic acid has demonstrated the broadest activity in this setting, and is approved for the prevention of skeletal-related events from bone metastases from a variety of solid tumors in addition to breast cancer and multiple myeloma. Ongoing studies are evaluating the antiresorptive potentials o Read More

Bisphosphonates are commonly used in patients with breast cancer to reduce skeletal-related events in metastatic disease and to mitigate bone loss associated with cancer therapy in early stage disease. In addition, adjuvant breast cancer trials evaluating the oral bisphosphonate clodronate suggested a reduction in cancer recurrence, but the findings were mixed, with 2 positive and 1 negative report. In the Austrian Breast a Read More

Lapatinib, a dual EGFR/HER2 kinase inhibitor, is approved for use in patients with trastuzumab-refractory HER2- overexpressing breast cancer. Increased PI3K signaling has been associated with resistance to trastuzumab, although its role in lapatinib resistance remains unclear. The purpose of the current study was to determine if PI3K/mTOR activity affects lapatinib sensitivity. Reduced sensitivity to lapatinib was associated w Read More

KRAS and BRAF mutations lead to the constitutive activation of EGFR signaling through the oncogenic Ras/Raf/Mek/Erk pathway. Currently, KRAS is the only potential biomarker for predicting the efficacy of anti-EGFR monoclonal antibodies (mAb) in colorectal cancer (CRC). However, a recent report suggested that the use of cetuximab was associated with survival benefit among patients with p.G13D-mutated tumors. Furtherm Read More

Procathepsin D (pCD) is overexpressed and secreted by cells of various tumor types including breast and lung carcinomas, affecting multiple features of tumor cells including proliferation, invasion, metastasis and apoptosis. As more and more attention has been focused on potential use of pCD in clinical practice, we devoted this paper to summarize the three major potentials of pCD—tumor marker, potential drug and scr Read More