The v8-10 variant isoform of CD44 is selectively expressed in the normal human colonic stem cell niche and frequently is overexpressed in colon carcinomas during tumor development.

CD44 protein and its variant isoforms are expressed in cancer stem cells (CSCs), and various CD44 isoforms can have different functional roles in cells. Our goal was to investigate how different CD44 isoforms contribute to the emergence of stem cell (SC) overpopulation that drives colorectal cancer (CRC) development. Specific CD44 variant isoforms are selectively expressed in normal colonic SCs and become overexpressed in CRCs during tumor development.

Survival Outcomes of Sipuleucel-T Phase III Studies: Impact of Control-Arm Cross-Over to Salvage Immunotherapy.

Sipuleucel-T is an autologous cellular immunotherapy for asymptomatic/minimally symptomatic metastatic castrate-resistant prostate cancer (CRPC). After disease progression, control-arm patients on three double-blind, randomized phase III sipuleucel-T trials were offered, in nonrandomized open-label protocols, APC8015F, an autologous immunotherapy made from cells cryopreserved at the time of control manufacture. These exploratory analyses evaluated potential effects on survival outcomes associated with such treatment.

A pilot phase II Study of digoxin in patients with recurrent prostate cancer as evident by a rising PSA.

Background: Digoxin was found to inhibit prostate cancer (PCa) growth via the inhibition of HIF-1α synthesis in a mouse model. We hypothesized that a therapeutic dose of digoxin could inhibit human PCa growth and disease progression.

Methods: An open label, single arm pilot study was performed.

A community computational challenge to predict the activity of pairs of compounds.

Recent therapeutic successes have renewed interest in drug combinations, but experimental screening approaches are costly and often identify only small numbers of synergistic combinations. The DREAM consortium launched an open challenge to foster the development of in silico methods to computationally rank 91 compound pairs, from the most synergistic to the most antagonistic, based on gene-expression profiles of human B cells treated with individual compounds at multiple time points and concentrations. Using scoring metrics based on experimental dose-response curves, we assessed 32 methods (31 community-generated approaches and SynGen), four of which performed significantly better than random guessing.

A community effort to assess and improve drug sensitivity prediction algorithms.

Predicting the best treatment strategy from genomic information is a core goal of precision medicine. Here we focus on predicting drug response based on a cohort of genomic, epigenomic and proteomic profiling data sets measured in human breast cancer cell lines. Through a collaborative effort between the National Cancer Institute (NCI) and the Dialogue on Reverse Engineering Assessment and Methods (DREAM) project, we analyzed a total of 44 drug sensitivity prediction algorithms.

Targeting epigenetics for the treatment of prostate cancer: recent progress and future directions.

Epigenetic aberrations contribute to prostate cancer carcinogenesis and disease progression. Efforts have been made to target DNA methyltransferase and histone deacetylases (HDACs) in prostate cancer and other solid tumors but have not had the success that was seen in the hematologic malignancies. Oral, less toxic, and more specific agents are being developed in solid tumors including prostate cancer.

Targeting angiogenesis as a promising modality for the treatment of prostate cancer.

Antiangiogenic therapy has been successful for the treatment of solid tumors. Several strategies have been used to target angiogenesis in prostate cancer. These strategies include blocking proangiogenic factors via monoclonal antibodies or small molecule inhibitors targeting downstream signaling effector pathways, or using agents with immune-modulatory effects.

HIF-1alpha and calcium signaling as targets for treatment of prostate cancer by cardiac glycosides.

Prostate cancer possesses its unique feature of low proliferation rate and slow growth. Ca(2+)-induced apoptosis is not dependent on cell cycle progression and targeting this pathway could circumvent the problems encountered using current cytotoxic chemotherapies for prostate cancer. Hypoxia-inducible factor 1alpha (HIF-1alpha) is another novel cancer drug target and inhibitors of hypoxia-response pathway are being developed.

Current prostate cancer treatments: effect on quality of life.

Patients with prostate cancer (PCa) are presented with multiple therapeutic options. However, the evidence supporting a survival benefit with current PCa therapies is often limited and data directly comparing the available options are lacking. Although dramatic improvements have been made in the treatment methods available for PCa and there has been a decline in death rates for the disease, each active intervention has potential side effects and long-term complications that can adversely affect quality of life (QOL).