Velcade approved for use in Canada

Health Canada has approved VELCADE (bortezomib) for Injection for the treatment of patients with multiple myeloma who have relapsed following front-line therapy and are refractory (unresponsive) to their most recent therapy. In a preliminary uncontrolled (Phase II) clinical trial in patients with multiple myeloma, VELCADE demonstrated a median survival of 16 months.

VELCADE was approved under Health Canada’s Notice of Compliance with Conditions Policy that enables physicians and their patients to gain early access to promising new therapies demonstrating clinical effectiveness. VELCADE is the only approved treatment for patients with multiple myeloma who have failed front-line therapy and are unresponsive to their most recent therapy.

VELCADE is a new kind of medication that has been specifically developed to fight cancer by blocking the proteasome, a structure that exists in all cells and plays an important role in breaking down proteins that control how the cell lives and grows. By blocking the proteasome, VELCADE disrupts processes related to the growth and survival of cancer cells. The scientists who conducted the research leading to the development of VELCADE received a Nobel Prize in chemistry in October 2004.

“When multiple myeloma patients fail two previous lines of therapy their cancer is one of the most difficult to treat,” says Dr. Keith Stewart, medical oncologist in Toronto and associate professor, department of medical oncology at the University of Toronto. “But with VELCADE, for the first time, we’re able to give these patients another option which in some cases can extend their lives.”

Research suggests that VELCADE may slow or halt progression of the disease in some patients. In a phase II study of 202 patients, 28 per cent responded to VELCADE.

“This is very encouraging data,” says Dr. Pierre Laneuville, McGill University Health Center Director of Hematology. “It suggests that VELCADE has shown effectiveness in almost three out of 10 multiple myeloma patients who have failed two previous lines of therapy. This should bring renewed hope to multiple myeloma patients and their families.”

Nanoparticles fight Myeloma

Anticancer drug efficiency is governed by its bioavailability. In order to increase this parameter, we synthesized several injectable and biodegradable systems based on incorporation of anti-estrogens (AEs) in nanoparticles (NPs) and liposomes were synthesized. Both nanospheres (NS) and nanocapsules (NCs, polymers with an oily core in which AEs were solubilized) incorporated high amounts of 4-hydroxy-tamoxifen (4-HT) or RU 58668 (RU). Physico-chemical and biological parameters of these delivery systems, and coupling of polyethylene-glycol chains on the NP surface revealed to enhance the anti-tumoral activity of trapped AEs in a breast cancer MCF-7 cell xenograft model and to induce apoptosis. These features correlated with an augmentation of p21(Waf-1/Cip1) and of p27(Kip1) and a concomitant decrease of cyclin D1 and E in tumor extracts.

Liposomes containing various ratios of lipids enhanced the apoptotic activity of RU in several multiple myeloma (MM) cell lines tested by flow cytometry. MM cell lines expressed both estrogen receptor alpha and beta subtypes except Karpas 620. Karpas 620 cells which did not respond to AEs became responsive following ER cDNA transfection. A new MM xenograft model was generated after s.c. injection of RPMI 8226 cells in nude mice. RU-loaded liposomes, administered i.v. in this model, at a dose of 12mgRU/kg/week, induced the arrest of tumor growth contrary to free RU or to empty liposomes. Thus, the drug delivery of anti-estrogens enhances their ability to arrest the growth of tumors which express estrogen receptors and are of particular interest for estrogen-dependent breast cancer treatment. In addition it represents a new potent therapeutic approach for multiple myeloma.

The Journal of Steroid Biochemistry and Molecular Biology
Volume 94, Issues 1-3 , February 2005, Pages 111-121

Gene therapy in cancer using viruses

Researchers at Columbia University Medical Center have discovered a way to overcome one of the major hurdles in gene therapy for cancer: its tendency to kill normal cells in the process of eradicating cancer cells.

In a new study published in the January 25 issue of the Proceedings of the National Academy of Sciences (PNAS), the researchers demonstrated that the technique works by incorporating it into a specially designed virus. The virus eradicated prostate cancer cells in the lab and in animals while leaving normal cells unscathed.

Gene therapy based on the new technique should also be effective for a wide range of tumors - such as ovarian, breast, brain, skin (melanoma) and colon cancer - because the virus is constructed to exploit a characteristic of all solid cancers.

The virus's selectivity for cancer cells is based on two molecules called PEA-3 and AP-1 that, the researchers found, are usually abundant inside cancer cells. Both of the molecules flip a switch (called PEG) that turns on the production of a cancer-inhibiting protein uniquely in tumor cells. The researchers say the PEG switch can be exploited to produce gene therapies that will only kill cancer cells even if the therapy enters normal cells. As an example, the researchers constructed an adenovirus that carries the PEG switch and a toxic protein. The switch and the protein were connected to each other so that the deadly protein is only unleashed inside cancer cells when the switch is flipped on by PEA-3 or AP-1. When added to a mix of normal and prostrate cancer cells, the virus entered both but only produced the toxic protein inside the cancer cells. All the prostrate cancer cells died while the normal cells were unaffected.

The same virus also selectively killed human cancer cells from melanoma and ovarian, breast, and brain tumors.

Dr. Fisher's team is now altering the virus and developing additional viruses based on the PEG switch for use in clinical trials with patients.

Mystery compound in beer fights cancer

Some cancers are caused by heterocyclic amines, DNA-damaging chemicals found in cooked meat and fish. When Sakae Arimoto-Kobayashi's team at Okayama University in Japan fed these chemicals to mice, the DNA damage to their liver, lungs and kidneys was reduced by up to 85% if the mice drank non-alcoholic beer instead of water.

Arimoto-Kobayashi thinks as-yet unidentified compounds in lager and stout prevent the amines binding to and damaging DNA. If these compounds can be identified, brewers might be able to produce beers particularly rich in them, or they could be added to foods.

Heavy alcohol consumption is blamed for around 6% of all cancers in western countries (New Scientist print edition, 18 December 2004), though moderate consumption reduces the risk of heart disease. Since the mice drank non-alcoholic beer, the findings do not show whether moderate consumption of normal beer has any anti-cancer benefits. "The total benefits and risks of beer with alcohol are still under consideration," says Arimoto-Kobayashi.

Journal reference: Journal of Agricultural and Food Chemistry (DOI: 10.1021/jf049208k)
New Scientist Print Edition