Researchers at the Moores Cancer Center at the University of California, San Diego (UC SD) in La Jolla have found evidence explaining why a common chemotherapyterm drug, cisplatin, may not always work for every cancer patient. They have shown that when a variant version of a key protein that normally causes cell death is active, patients may be resistant to the cancer-killing drug.

The scientists say that such findings, reported online this week in the journal Proceedings of the National Academy of Sciences, are important to understanding how personalized therapies may be developed for patients.

Platinum complexes such as the well-known cisplatin are powerful antitumor medications. They cross the cell membrane and reach the nucleus, where they attach to DNA and stop cell growth. But how does cisplatin get to the nucleus? Italian researchers have now proven that a copper transport protein may play a critical role. In the journal Angewandte Chemie, they present their hypothesis about the transport mechanism.

It has always been assumed that cisplatin simply passes through the cell membrane; however, growing evidence indicates that a copper transporter is involved. Ctr1 is a membrane-dwelling protein that brings copper into cells. It consists of three helical segments that sit in the membrane, one end protruding into the cell, the other on the outside. Three such molecules lodge together to form a channel-like structure. The end that sticks out of the cell and the interior of the “channel” contain many sulfur-containing methionine groups, which are important for binding copper.

New scientific evidence is helping to build a compelling case for oncolytic viruses as a first-line and adjunctive treatment for many cancers.

Reovirus, a non-pathogenic virus under development at Calgary, Alberta-based Oncolytics Biotech, has shown powerful anti-cancer activity against cultured tumor cells, in animal models, and in human clinical trials. Oncolytics' proprietary reovirus formulation, Reolysin®, is active against numerous cancers, including intractable sarcomas and melanomas.

Recent studies also indicate that Reolysin works synergistically with standard anti-cancer drugs, providing significantly stronger responses than either agent alone.

    Antisoma, a London based company, announced at the ASCO Prostate Cancer Symposium positive phase II trial interim results in hormone-refractory prostate cancer patients in a combination treatment with AS1404. The results showed that PSA response rates were higher in the AS1404-docetaxel combination (57%) than with docetaxel alone (35%). Time to tumor progression and survival data will be reported later in the year, but current data shows that the frequency of PSA progression was halved in the AS1404-docetaxel combination versus docetaxel alone (17% versus 29%). Safety statistics indicate no significant increase in side-effects from AS1404.

    Marshall R. Posner, MD, medical director of the Head and Neck Oncology Program at the Dana-Farber Cancer Institute in Boston reported at the 2006 annual meeting of the American Society of Clinical Oncology (ASCO) on the randomized Phase III TAX 324 Study Group. 501 patients with locally advanced squamous cell carcinomaterm of the head and neck (SCCHN) (oral cavity, oropharynx, larynx and hypopharynx) were the focus of the study.

    Transitional cell carcinomaterm (TCC) of the urothelium (these are epithelial cells that mainly line the urinary tract) is usually treated with a combination regimen of methotrexate/vinblastine/doxorubicine/cisplatin (known as M-VAC). Recent reports from a phase III trial showed that M-VAC versus gemcitabine plus cisplatin (GC) had similar response rates, time to progression and overall survival. However, GC was less toxic than M-VAC and the need for overall survival improvement needed to be increased. This article presents a phase II study of a combination of gemcitabine and docetaxel. Gemcitabine [Gemzar from Eli Lilly] is a DNA analogue that inhibits DNA synthesis ultimately leading to cell death. Docetaxel [Taxotere from Sanofi Aventis] is a paclitaxel analogue that stabilizes tubulin ultimately preventing cellular division and leading to cell death. These two drugs are thought to have a synergistic effect. That is, the combination effect of the two drugs is greater than that predicted from the effects from single drug therapy.

    The trial included 34 patients with advanced TCC that was unresectable for cure or had measurable metastasistermterm were non-randomly selected with primary tumor sites being 26 bladder, 5 kidney, and 3 ureter. 7 patients had previous chemotherapyterm (21%). 82% had previous surgery to remove the primary tumor, with 20 patients having some form of metastasis. Haematologic (blood) toxicity was common during treatment (24% in some side effectsterm). A complete response (CR) was seen in 2 patients (5.8%) where all lesions or growths disappeared. A partial response (PR) was seen in 16 patients where the lesion or growth size was decreased by 30% or more. This gave an overall response rate (OR) of 53%. One aspect the study noted was a shift in the distribution of gemcitabine from the plasmid to the red blood cells (RBC).
One part the researchers note in the study is the high OR rate. Other studies of this combination of drug have shown OR rates of 17% as a second line and 33% as a first line of treatment. The researchers suggests the reason for the better response rate in their study is their study has a larger number of patients who have never been treated with chemo drugs (chemotherapy-naïve) and has a more favorable drug administration schedule.