Abstract: Although thyroid carcinoma usually has an excellent prognosis, the lack of therapeutic options is an issue for patients that develop metastases and are resistant to radioiodine therapy. The development of novel molecular targeted therapies and the characterization of several proteins that have a crucial role in the carcinogenesis process of differentiated thyroid cancer have created an opportunity to design new clinical trials for this setting. Moreover, the encouraging initial results of first clinical trials have accelerated the development of placebo-controlled phase III studies that will assess the role of these new agents in the management of differentiated thyroid cancer. ... Read more

Abstract: Treatment outcome for advanced-stage non-small cell lung cancer (NSCLC) is limited by empiric administration of cytotoxic chemotherapy. Recent advances in molecular genomics have revolutionized cancer management and, specifically, epidermal growth factor receptor (EGFR) mutation has become a potent biomarker for lung cancer, which predicts tumor response to and prolonged duration of disease control by EGFR tyrosine kinase inhibitors (TKI). The Iressa Pan-Asia Study (IPASS) is a randomized phase III study comparing gefitinib (EGFR TKI) with paclitaxel/carboplatin (standard chemotherapy) in Asian non-/light smokers with adenocarcinoma. Progression-free survival (PFS) in EGFR mutation-positive patients was longer with gefitinib than with chemotherapy (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.36-0.64; p<0.0001); in EGFR mutation-negative patients, PFS was longer with chemotherapy than with gefitinib (HR 2.85; 95% CI 2.05-3.98; p<0.0001). The findings are confirmed by one single-arm study and three other randomized studies. It has become clear that personalized medicine for NSCLC is feasible. This small step towards personalized medicine represents a paradigm shift in the management of NSCLC. ... 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

Abstract: Certain mutations in the epidermal growth factor receptor (EGFR) gene confer hypersensitivity to the tyrosine kinase inhibitors gefitinib and erlotinib in patients with advanced non-small cell lung cancer. Large-scale screening for EGFR mutations in such patients is feasible for predicting response to TKIs and thus guiding treatment. ... Read more

Abstract: One of the major advances in cancer therapy in recent years is the targeted killing of tumor cells. ERBB receptor tyrosine kinase is expressed on many types of cancer cells and has been proven to be an effective target. ERBB targeted antibodies versus small-molecule kinase inhibitors are compared. ... Read more

Abstract: Heat shock protein 90 (Hsp90) proves to be one of the few cancer drug targets that are cancer-specific and are less likely to induce drug resistance over time. Though universally present, Hsp90 assumes a special shape in cancer cells and hence becomes a unique target. Because of its critical role in cell survival, it does not often mutate and therefore it is not prone to drug resistance. ... Read more

On April 26, 2004, OSI Pharmaceuticals, Melville, NY, together with its development and marketing partners Genentech, S. San Francisco, CA and Roche, Basel, Switzerland, announced that a Phase III study of Tarceva (erlotinib HCl), an investigational human endothelial growth factor receptor (HER1/EGFR)-inhibitor drug in patients with non-small cell lung cancer (NSCLC), met its primary endpoint of improving overall survival, with the patients receiving Tarceva living longer than those in the placebo arm of the study. The trial also met secondary endpoints including improving the time to symptomatic deterioration, progression-free survival and response rate. Patients enrolled in the study were previously ... Read more

In a major advance in the field of personalized medicine, two clinical research groups illustrated the underlying pharmacogenetic mechanism for why most EGFR-expressing non-small cell lung cancer (NSCLC) patients do not respond to Iressa and why a small percentage (10%) of these patients responded to it dramatically. The study results indicated that the quantity of the EGFR (overexpression) isn’t important, but it’s the quality (alterations by mutations) that counts with regard to the response behavior of these tumor cells to Iressa, which is a small molecule EGFR inhibitor made by AstraZeneca approved by the U.S. FDA last May.

A team of ... Read more

Kinases: The Target

In 1983, Alex Matter, the “Bulldozer”, was recruited as the head of the newly established Oncology Unit in Ciba-Geigy, Basel, Switzerland. At that time, cancer research programs were not taken seriously, perhaps rightfully so: No drugs for cancer worked, so the vast majority of people died. While other physician specialists cured or made patients feel better, oncologists, in trying to help patients with cancer drugs, usually made patients’ lives more miserable. With the “carpet bombing” approach, chemotherapy destroyed everything in its path, both cancerous and normal cells. Chemotherapy weakened patients and hardly improved the quality of the patients’ ... 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