Genetic Abnormalities Predict Prostate Cancer Survival

Researchers have discovered that the combination of three genetic abnormalities significantly impacts how long a prostate cancer patient is likely to survive with the disease, according to the latest edition of the British Journal of Cancer.

Scientists at The Institute of Cancer Research (ICR) believe that patients could be tested for these genetic abnormalities to help decide the intensity of treatment they should receive.

The team used a technique called fluorescence in situ hybridisation (FISH) to examine three specific genetic alterations in prostate cancer samples from 308 patients: loss of the PTEN gene and rearrangement of the ERG or ETV1 genes.

Previous studies have shown that ERG gene rearrangements occur commonly in prostate cancer as do deletions of all or part of the PTEN gene, but the combined impact of these abnormalities on survival in a large group of patients has not previously been examined.

Study lead author and ICR scientist Dr Alison Reid says the presence or absence of these abnormalities has a major impact on a patient’s risk of dying from prostate cancer.

“In this study, we found that patients who had none of these genetic alterations had a good prognosis – 85.5 per cent were still alive after 11 years,” Dr Reid says. “Happily, the majority of prostate cancer sufferers in this study, 54 per cent, were in this category.” Read more

Agents Targeting Prostate Cancer Bone Metastasis

UroToday.com – Advanced prostate cancers regularly metastasize to the skeleton, and better treatments are needed to decrease morbidity and increase survival in men with end-stage disease. Metastatic prostate cancer cells alter the bone microenvironment in two ways:

1) they stimulate formation of disorganized new bone with poor biomechanical quality;

2) they stimulate bone remodeling by activating osteoclasts.

These two steps offer unique adjuvant targets to supplement conventional anti-tumor therapies. Drugs against osteoclasts include classes of anti-resorptive agents developed against osteoporosis. In addition to the approved bisphophonates, inhibitors are in Phase III trials against osteoclast-selective targets cathepsin K and RANK ligand. Pathological bone in osteoblastic lesions may be caused by prostate-secreted endothelin-1, whose actions are blocked by endothelin receptor antagonists in Phase III trials. The status of these drugs is reviewed in the linked title article. Bone metastases provide a novel paradigm for cancer treatment: adjuvant therapy aimed at the metastatic microenvironment (rather than the tumor itself) can reduce tumor burden and decrease morbidity and mortality. Such therapy can increase the efficacy of conventional cytotoxic agents to kill tumor within bone (1,2), where it is otherwise resistant to treatment. The next step beyond the abstract is to develop more adjuvant therapies that target the microenvironment. The agents described above were developed for non-cancer indications: anti-resorptives for osteoporosis and endothelin antagonists for pulmonary hypertension. They were easily tested in animal models and rapidly brought to clinical trials, since their pharmacokinetics and safety profiles were known. How will we go about testing new mechanisms? For example, the authors have preliminary data that the tumor-secreted peptide adrenomedullin might be a good target for adjuvant therapy, but there are no drugs ready to test in laboratory animals, which is also a slow and expensive approach. Direct anti-tumor drugs are first tested against growth of tumor cells in vitro, but bone metastases do not form in vitro. It would be risky to develop drugs in vitro to find out that the drug target was not important in vivo. Read more

Primary Endpoint Reached In Active Biotech’s TASQ Phase II Clinical Trial In Prostate Cancer Patients

A first analysis of the primary endpoint based on data from at least six months’ treatment of more than 200 patients, has been performed in Active Biotech AB’s (NASDAQ OMX Nordic: ACTI) ongoing Phase II clinical study of TASQ, in patients with asymptomatic, castrate resistant, metastatic prostate cancer.

In this analysis, safety, efficacy and certain biomarkers were evaluated. The primary endpoint, to show a difference in the number of patients with disease progression at six months, was reached. The fraction of patients with disease progression during the six month period was 43 % for patients treated with TASQ compared to 67 % for placebo treated patients. The median progression free survival was 24.7 weeks for the TASQ group, compared to 12.9 weeks (p=0.0001) for the placebo group. TASQ treatment also had a positive effect on several biomarkers relevant for prostate cancer progression and was generally well tolerated. No safety concerns significantly affecting the risk/benefit ratio for TASQ were identified.

“This is a very important milestone for TASQ and Active Biotech. I am looking forward to the further development of this novel, non-cytotoxic treatment. “, says Professor Tomas Leanderson, CEO Active Biotech “. Read more

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