Drug resistance in metastatic castration-resistant prostate cancer.

Docetaxel in combination with prednisone is the standard of care in men with symptomatic castration-resistant prostate cancer (CRPC). However, a substantial proportion of men with CRPC do not benefit from docetaxel or other systemic therapy and those who do benefit invariably progress and die of (or with) prostate cancer. Resistance to chemotherapy in metastatic CRPC is a result of cellular mechanisms of drug resistance intrinsic to prostate cancer and general mechanisms common to different tumor types.

Effect of multikinase inhibitors on caspase-independent cell death and DNA damage in HER2-overexpressing breast cancer cells.

Background: The receptor tyrosine kinase, HER2, is overexpressed in approximately 25% of patients with breast cancer and is implicated in the aggressiveness of cancer. Targeting of HER2 signaling with trastuzumab, a monoclonal antibody that inhibits HER2 activity, has demonstrated clinical benefits.

Methods: We investigated whether the antitumor activity of trastuzumab can be potentiated by dasatinib, a small-molecule tyrosine kinase inhibitor, on breast cancer cell lines that overexpress HER2 (BT474 and SKBR3) or have normal HER2 expression (MCF7 and T47D).

Personalized therapies in the cancer "omics" era.

A molecular hallmark of cancer is the presence of genetic alterations in the tumoral DNA. Understanding how these alterations translate into the malignant phenotype is critical for the adequate treatment of oncologic diseases. Several cancer genome sequencing reports have uncovered the number and identity of proteins and pathways frequently altered in cancer.

Targeting DNA repair in breast cancer: a clinical and translational update.

DNA-repair mechanisms play an important role in the maintenance of DNA integrity and protection against DNA damage. Deregulation of these mechanisms is associated with the development of cancer as is seen in breast tumours with mutations in genes like BRCA1 and BRCA2. Recent biologic findings suggest that in tumours in which one DNA repair pathway is deficient, concomitant inhibition of other repair pathways could have potential synergistic activity.

In vitro study of the effect of diesterified alkoxyglycerols with conjugated linoleic acid on adipocyte inflammatory mediators.

Background: Adipocytes contribute to inflammation and the innate immune response through expression of inflammatory mediators. High levels of these mediators have been related to chronic inflammation state and insulin resistance, cardiovascular diseases and diabetes type 2, among other disorders. 3-octadecylglycerol (batyl alcohol) has been described as an inflammatory agent, whereas Conjugated Linoleic Acid (CLA) is considered effective against obesity.

Medical oncology: Zoledronic acid for breast cancer therapy-induced bone loss.

The addition of zoledronic acid to aromatase inhibitors is associated with improved bone mineral density, but not with an effect on clinically-meaningful end points such as fractures. The oncology community should prioritize the design of trials evaluating more relevant end points, such as fragility fracture risk, for treatment-induced bone loss and critically assess the effects of such treatment on breast cancer survival.

Lapatinib and HER2 status: results of a meta-analysis of randomized phase III trials in metastatic breast cancer.

Background: In vitro studies have shown that lapatinib is most active in HER2 over-expressing tumors, but also has activity in cell lines over-expressing HER1. Consequently, clinical testing of lapatinib has been carried out in both HER2-positive and HER2-negative patients. Here we evaluate the clinical efficacy of lapatinib in HER2-positive and HER2-negative patients.

Antioxidant activity, bioactive polyphenols in Mexican goats' milk cheeses on summer grazing.

Two feeding systems trials were carried out to determine the antioxidant activity of soft goats' milk cheeses, and also to evaluate the presence of bioactive polyphenolic compounds. Two groups (A and B), each one with 20 (BW 50+/-5 kg) French Alpine goats were employed. All animals had between 70 to 80 milking days and were milked once a day.

Irreversible pan-ErbB tyrosine kinase inhibitors and breast cancer: current status and future directions.

Aberrant activation of HER2 through overexpression has been shown to play an important role in some breast cancers. Therapies against this receptor including the monoclonal antibody, trastuzumab, or the small tyrosine kinase inhibitor, lapatinib have shown to improve the prognosis of such patients. Despite overexpressing HER2, some patients do not respond to these targeted treatments or progress after a short period of time.

Expression of Erk5 in early stage breast cancer and association with disease free survival identifies this kinase as a potential therapeutic target.

Background: Breast cancer is the most common neoplasia in women. Even though advances in its treatment have improved disease outcome, some patients relapse. Therefore, attempts to better define the molecular determinants that drive breast cancer cell proliferation may help in defining potential therapeutic targets.

An update on the biology of cancer stem cells in breast cancer.

Breast cancer stem cells are defined as cancer cells with self-renewal capacity. These cells represent a small subpopulation endowed with the ability to form new tumours when injected in nude mice. Markers of differentiation have been used to identify these cancer cells.

Synergic antitumoral effect of an IGF-IR inhibitor and trastuzumab on HER2-overexpressing breast cancer cells.

Background: Receptor tyrosine kinases play an important role in breast cancer. One of them, the type I insulin-like growth factor, has been linked to resistance to trastuzumab (Herceptin), an agent that targets human epidermal growth factor receptor 2. Here, we show that the insulin-like growth factor-I receptor (IGF-IR) antagonist NVP-AEW541 inhibits proliferation of breast cancer cells and synergizes with trastuzumab.

Neuregulins and cancer.

The neuregulins represent the largest subclass of polypeptide factors of the epidermal growth factor family of ligands. These molecules are synthesized as membrane-bound, biologically active growth factors that act by binding to the HER/ErbB receptor tyrosine kinases. Preclinical data have indicated that increased expression and function of neuregulins may provoke cancer.

Identifying breast cancer druggable oncogenic alterations: lessons learned and future targeted options.

Although the introduction of novel therapies and drug combinations has improved the prognosis of metastatic breast cancer, this disease remains incurable. It is therefore important to develop additional novel therapeutic strategies and agents. Increased understanding of the biology and the molecular alterations present in breast cancer is facilitating the design of targeted therapies directed to oncogenic proteins.

New options in the treatment of locally advanced head and neck cancer: role for induction chemotherapy.

Advanced locoregional disease is the most frequent clinical situation in Head and Neck cancer. The standard of care for most clinicians is a multidisciplinary treatment with concomitant chemotherapy plus radiotherapy (CRT). However, retrospective studies have shown that in patients treated with CRT there was a relative increase in systemic relapse due to a lack of systemic control.

Neuregulin expression modulates clinical response to trastuzumab in patients with metastatic breast cancer.

Purpose: Human epidermal growth factor receptor 2 (HER-2) overexpression has been associated with the genesis and progression of a subset of breast cancers. The function of HER-2 may be upregulated by overexpression or by the availability of neuregulins (NRGs), a group of transmembrane growth factors. Transmembrane NRGs strongly activated HER-2 and cell proliferation in breast cancer cells that did not overexpress HER-2, and treatment with trastuzumab prevented the proliferative action of transmembrane NRG.

Human recombinant erythropoietic agents do not induce changes in circulating levels of endoglin and vascular endothelial growth factor in anemic cancer patients.

The correlation of erythropoietin (EPO) receptor levels with angiogenesis and progression in some cancers has suggested that EPO could acts directly as an angiogenic factor. The purpose of this study was to assess the effect of treatment with human recombinant erythropoietic (rHuEPO) agents in cancer patients with chemotherapy-induced anaemia on endoglin and vascular endothelial growth factor (VEGF) circulating levels as a possible marker of angiogenesis. Endoglin and VEGF were measured in serum samples from 25 cancer patients with chemotherapy-induced anemia before and after 3-4 weeks of treatment with rHuEPO.

Expression of p95HER2, a truncated form of the HER2 receptor, and response to anti-HER2 therapies in breast cancer.

Background: Women with HER2-overexpressing breast cancers have poor prognosis, and many are resistant to the HER2 monoclonal antibody trastuzumab. A subgroup of HER2-overexpressing tumors also express p95HER2, an amino terminally truncated receptor that has kinase activity. Because p95HER2 cannot bind to trastuzumab but should be responsive to the HER2 tyrosine kinase inhibitor lapatinib, we compared the sensitivity of tumors expressing p95HER2 and tumors expressing the full-length HER2 receptor to these agents.