Virus Combination Effective Against Deadly Brain Tumor, Moffitt Cancer Center Study Shows

Main Category: Cancer / Oncology
Also Included In: Neurology / Neuroscience
Article Date: 24 Jun 2013 - 1:00 PDT Current ratings for:
Virus Combination Effective Against Deadly Brain Tumor, Moffitt Cancer Center Study Shows

A combination of the myxoma virus and the immune suppressant rapamycin can kill glioblastoma multiforme, the most common and deadliest malignant brain tumor, according to Moffitt Cancer Center research. Peter A. Forsyth, M.D., of Moffitt's Neuro-Oncology Program, says the combination has been shown to infect and kill both brain cancer stem cells and differentiated compartments of glioblastoma multiforme.

The finding means that barriers to treating the disease, such as resistance to the drug temozolomide, may be overcome. The study, by Forsyth and colleagues in Canada, Texas and Florida, appeared in a recent issue of Neuro-Oncology.

"Although temozolomide improves survival for patients with glioblastoma multiforme, drug resistance is a significant obstacle," said Forsyth, the study lead author. "Oncolytic viruses that infect and break down cancer cells offer promising possibilities for overcoming resistance to targeted therapies."

The authors note that oncolytic viruses have the potential to provoke a multipronged attack on a tumor, with the potential to kill cancer cells directly through viral infection and possibly through inducing the immune system to attack the tumor. The multipronged approach might get around some of the classical resistance mechanisms that have plagued both targeted therapies and conventional chemotherapies.

Several oncolytic viruses, both alone or in combination with small molecule inhibitors, have been tested and show promise for malignant gliomas. However, most have not been effective in killing cancer cells. Two likely obstacles may be the patient's own anti-viral immune response and limited virus distribution.

"Based on our previous work with myxoma virus, we considered it to be an excellent oncolytic virus candidate against brain cancer stem cells," explained Forsyth.

The researchers found that brain cancer stem cells were susceptible to myxoma virus in the laboratory cultures (in vitro) and in animal models (in vivo), including in temozolomide-resistant cell lines.

"We also found that myxoma virus with rapamycin is a potentially useful combination. The idea that cancer cells can be killed by a harmless virus is an exciting prospect for therapy," Forsyth said.

The precise mechanism rapamycin uses to enhance infection in brain cancer stem cells is unknown, and the combination therapy does not result in cures. However, researchers are investigating other drugs that may improve the effectiveness of myxoma virus when used in combination, and they are evaluating the use of other strains of myxoma virus that might be more effective.

"Although our study adds myxoma virus to the list of oncolytic viruses capable of infecting and killing these cells, which strengthens its candidacy for clinical application, our model will need clinical application to determine its safety for patients," concluded the authors. "We expect that intracranial injections of myxoma virus will be safe based on our extensive preclinical work and the demonstrated safety of other oncolytic viruses in clinical trials."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our cancer / oncology section for the latest news on this subject. This study was supported by grants from the National Institutes of Health (R01 AI080607, R21 CA149869, and R01 CA138541).

Researchers from the University of Florida, University of Calgary, University of Texas and Ottawa Regional Cancer Centre Research Laboratories contributed to this work and publication.

H. Lee Moffitt Cancer Center & Research Institute

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Combination of HER2-Targeted Therapies May Provide Breast Cancer Benefit

Among women with early, HER2-positive breast cancer, treatment with a combination of HER2-targeted therapies may produce better outcomes than treatment with only a single HER2-targeted therapy. This was the conclusion of two studies presented at the 2010 San Antonio Breast Cancer Symposium. One of the studies evaluated neoadjuvant (before surgery) HerceptinR (trastuzumab) plus TykerbR (lapatinib), and the other evaluated neoadjuvant Herceptin plus pertuzumab.

Approximately 20-25% of breast cancers overexpress (make too much of) a protein known as HER2. Fortunately, the development of drugs that specifically target HER2-positive breast cancer has improved outcomes. These drugs include Herceptin, Tykerb, and the investigational drug pertuzumab.

Combinations of HER2-targeted therapies have shown a benefit in studies of women with metastatic breast cancer (cancer that has spread to other parts of the body), and researchers are also evaluating these combinations in women with earlier-stage breast cancer.

The NeoALTTO study is a Phase III clinical trial that has enrolled 455 women with early, HER2-positive breast cancer.[i] The study was restricted to women with operable breast cancer greater than 2 cm in size; women with inflammatory breast cancer were excluded. Study participants were assigned to one of three neoadjuvant (before surgery) treatment groups:

Tykerb plus chemotherapyHerceptin plus chemotherapyHerceptin plus Tykerb plus chemotherapy

The primary outcome of the study was the pathological complete response (pCR) rate. A pCR refers to the disappearance of detectable cancer at the time of surgery. After surgery, patients received additional chemotherapy and HER2-targeted therapy.

Response rates were highest among women treated with the combination of Herceptin and Tykerb: a pCR was achieved by 51.3% of women in the combined Herceptin/Tykerb group, 29.5% of women in the Herceptin group, and 24.7% of women in the Tykerb group.

In a second study, a Phase II clinical trial known as NeoSphere, researchers enrolled 417 women with Stage II or Stage III HER2-positive breast cancer.[ii] Study participants were assigned to one of four neoadjuvant treatment groups:

Herceptin plus chemotherapyHerceptin plus pertuzumab plus chemotherapyHerceptin plus pertuzumab (without chemotherapy)Pertuzumab plus chemotherapy

After surgery, patients received additional chemotherapy and Herceptin.

Response rates were highest among women treated with the combination of Herceptin, pertuzumab, and chemotherapy. A pCR was achieved by 45.8% of women treated with all three drugs, 29% of women treated with Herceptin plus chemotherapy, 24% of women treated with pertuzumab plus chemotherapy, and 16.8% of women treated with Herceptin plus pertuzumab without chemotherapy.

Taken together, these studies suggest that a combination of HER2-targeted therapies may be most effective against HER2-positive breast cancer.? While these data are very encouraging, both studies were small and we do not know that the improvement in pCR will result in fewer recurrences or longer survival.? At this point, these studies should stimulate additional research, but they should not be used as evidence to change clinical practice standards.

[i] Baselga J, Bradbury I, Eidtmann H et al. First results of the NeoALTTO Trial (BIG 01-06/EGF 106903): A phase III, randomized, open label, neoadjuvant study of lapatinib, trastuzumab, and their combination plus paclitaxel in women with HER2-positive primary breast cancer. Presented at the 33rd annual San Antonio Breast Cancer Symposium, December 8-12, 2010. Abstract S3-3.

[ii] Gianni L, Pienkowski T, Im Y-H et al. Neoadjuvant pertuzumab (P) and trastuzumab (H): antitumor and safety analysis of a randomized phase II study (‘NeoSphere’). Presented at the 33rd annual San Antonio Breast Cancer Symposium, December 8-12, 2010. Abstract S3-2.

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