Abstract: Despite the recent advances in its management using cytoreductive surgery and chemotherapy, ovarian cancer remains the most lethal gynecological malignancy. One possible treatment strategy that may improve patient outcome is the use of monoclonal antibodies (mAb) that selectively target tumor cells expressing tumor-associated antigens, and thus offer potential benefits such as avoiding the cytotoxic side effects in normal tissue caused by traditional chemotherapeutic agents. Based on the promising results of preclinical studies, various mAb are currently being evaluated in patients with ovarian cancer. Some of them have already demonstrated favorable clinical outcomes in phase I/II studies. However, in contrast to its use for hematological malignancies and certain solid malignancies such as breast and colorectal cancer, mAb-based therapy has not been convincingly proven to be clinically effective in patients with ovarian cancer. As the preclinical results of mAb's therapeutic effects on ovarian cancer have been encouraging, further investigations are needed to establish a more effective, specific, and less toxic treatment strategy for this malignancy. ... Read more

Abstract: Age-related Macular Degeneration (AMD) is the major cause of vision loss after age 50 in the United States. Although an important association of the complement cascade with AMD has recently been made, we still do not understand the pathogenesis of the disease. AMD is characterized by loss of the retinal pigment epithelium (RPE) within the macula (i.e., the center of the retina), and in turn, loss of the overlying foveal photoreceptors. Since RPE and photoreceptors can both be generated from stem cells using cell culture, there is hope for future cell replacement therapy. But, aging changes in Bruch's membrane, the scaffold on which the RPE are anchored, may complicate such therapy, and require surgical repair of Bruch's membrane to provide a suitable environment for cell survival and function. We have referred to such a multipronged approach of surgical reconstruction of the macular architecture in conjunction with cell transplantation as Maculoplasty. ... Read more

Abstract: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. About 50% of the patients present locally advanced or metastatic disease at the time of diagnosis. First line therapy usually consists of a combination of cisplatin or carboplatin with a third-generation agent (paclitaxel, docetaxel, gemcitabine, or vinorelbine) that results in less than 5% 5-year survival (Goldstraw et al., 2007). Recently a different approach based on histological subtype has been introduced in the first line treatment of NSCLC: in the non-squamous histotypes, cisplatin plus pemetrexed, compared to the cisplatin plus gemcitabine combination, showed a better outcome, leading to its introduction in the first line treatment setting. In recent years advances in the second and third line treatments have led to a prognostic improvement. Two cytotoxic agents, docetaxel and pemetrexed, are approved as NSCLC second line treatment, and a new class of drugs against specific molecular targets -- tyrosine Kinase inhibitors (TKI) -- has emerged as an alternative to conventional treatment. Many trials are ongoing to assess the activity of new drugs, alone or in combination with other agents, or new combinations of third-generation chemotherapeutic agents. ... Read more

Other Names: bevacizumab, rhuMAb-VEGF.

Maker: Genentech, Inc.

Disease Treated: Metastatic colorectal cancer.

Approval Status: Approved by the U.S. FDA on February 26, 2004 as a first-line therapy in combination with intravenous 5-fluorouracil-based chemotherapy for the treatment of metastatic colorectal cancer.

Chemical/Biological Nature: AVASTIN is a recombinant humanized monoclonal IgG1 antibody composed of the human antibody framework regions integrated with the complimentarity-determining regions (in contact with its target antigen) of mouse origin. AVASTIN is produced in a Chinese Hamster ovary mammalian cell expression cell culture system.

Administration: AVASTIN with a dose of 5mg/kg body weight is administered by i.v. infusion over a 90-minute period following chemotherapy. ... Read more

On Feb. 26, 2004, Genentech, S. San Francisco, CA announced that the U.S. FDA has approved Avastin (bevacizumab) to be used in combination with intravenous 5-fluorouracil-based chemotherapy as a first-line treatment for patients with metastatic colorectal cancer. Avastin is an angiogenesis inhibitor that blocks the process by which new blood vessels develop, a necessary requirement for tumor growth and metastasis. It is the first of this category of drugs to be approved by the FDA. Illustrating its readiness and commercial preparation, Genentech said it would begin shipping Avastin within three calendar days following the approval.

Avastin is a humanized monoclonal antibody ... Read more

On Feb. 12, 2004, the U.S. FDA approved Erbitux (cetuximab), a first-of-its-kind antibody drug, for use in combination with irinotecan (Camptosar) in the treatment of patients with epidermal growth factor receptor-expressing, metastatic colorectal cancer who are refractory to irinotecan-based chemotherapy and for use as a single agent in the treatment of patients who are intolerant to irinotecan-based chemotherapy. “Cetuximab validates the concept that non-chemotherapeutic molecular drugs are active in the treatment of colorectal cancer,” said Howard Hochster, M.D., Professor of Medicine, New York University School of Medicine. “It adds a new dimension in the treatment of this disease and allows ... Read more

On May 19, 2003, Genentech announced that its anti-cancer drug Avastin “markedly” improved overall survival when combined with standard chemotherapy in a phase III clinical trial of colon cancer patients. Details of the trial were made available at the American Society of Clinical Oncology’s (ASCO) Annual Conference held in Chicago in early June (see below), though the few tidbits that were released on May 19 have proven to be especially juicy. Genentech stock was up 45% or an increase of $8.7 billion in market value following the news. The excitement lived on. In the ensuing days, Genentech stock was up ... Read more

Dr. Judah Folkman has a mission: killing cancer cells by starving them. In 1967 at the age of 34, when Dr. Folkman became the youngest professor of surgery at Harvard Medical School, he had already begun formulating the concept of angiogenesis in cancer. In the following 30 years, Dr. Folkman and others documented the importance of angiogenesis in cancer growth and the significance of angiogenesis as a cancer treatment target.

Collectively, these studies formed a powerful thesis for angiogenesis-based cancer therapy. The thesis goes as follows.

1. Tumor growth is dependent on angiogenesis. Microvascular endothelial cells lining the capillaries are essential for ... Read more

In a pronounced backdrop of Wall Street sentiment that is obsessed with real and perceived worries, capital valuation of biotech and pharmaceuticals companies contracted last month (from August 15th to September 15th) (please see the table for sector indexes). Biotech and pharmaceutical companies were also confronted with their own problems. Product disappointments added to the negative tone.

On September 10, 2002, Genentech announced that its Avastin, a drug that targets the angiogenesis in tumors, failed to prolong the life of breast cancer patients in a large phase III pivotal trial. Genentech has looked upon the drug as the future engine for ... Read more

Genentech reported on September 10th that its angiogenesis drug Avastin did not improve survival among 462 late stage breast cancer patients who had previously failed all other therapies. Genentech said that Avastin did shrink tumors in some patients but that the shrinkage did not offer survival benefits.

Scientists believe that the concept to choke off the tumor growth by deterring angiogenesis is still a sound approach in fighting cancer. But recently they grew increasingly skeptical whether blocking a single angiogenesis factor would do the trick. Scientists have found that late stage cancer cells, breast cancer in particular, can make as many ... Read more