Novel Cytotoxic Agents for Non-small Cell Lung Cancer

Abstract

Cytotoxic agents have unequivocal activity in non-small cell lung cancer. Currently available agents have demonstrated the ability to prolong life and improve quality of life in advanced disease, and to increase the rate of cure when used in stage I and II disease in the adjuvant setting and as part of chemoradiotherapy in stage III disease. These agents have served as the core regimen to which agents effecting newly discovered molecular targets are added. However, there is little question that there is much room for improvement. A number of new agents have been identified that either derive from older drugs or affect their targets in novel ways. In particular, tubulin has been an attractive target since the dawn of medical oncology. A number of new antitubulin agents are currently in development. Epothilones are novel agents that bind to the same site as taxanes, yet are structurally distinct. Xyotax and abraxane are agents in which paclitaxel is delivered in a novel fashion that may both reduce toxicity and enhance activity. ABT 751 is an agent that targets the colchicine site of tubulin. Another approach is to enhance the activity of currently available agents by targeting detoxification and resistance pathways. TLK-286 is a novel agent that may enhance the activity of previously available agents by inhibiting GST-pi, a detoxifying mechanism that may be of particular relevance to platinum agents. It has also demonstrated some single-agent cytotoxic activity.

The mechanisms of nadroparin‐mediated inhibition of proliferation of two human lung cancer cell lines

“…Figure shows that nadroparin treatment did not modulate p21 expression, as assessed by western blotting. In contrast, colchicine [a known inhibitor of tubulin polymerization in cells, including non‐small cell lung cancer cells ] used as a positive control, caused upregulation of p21 levels, as expected. This result demonstrates that G 2 /M phase arrest by nadroparin in A549 cells is not dependent on the p21 pathway.…”

Identification of novel target proteins in sebaceous gland carcinoma

“…A new target agent named telcyta (TLK)‐286 may hold promise by increasing tumor sensitivity to platinums. TLK‐286 has demonstrated cytotoxic activity on its own,22 but through its inhibition of Gstπ it can enhance the activity of cisplatin in cancer cells 23. A Gstπ inhibitor such as TLK‐286 may hold promise in patients with sebaceous gland carcinoma through its ability to sensitize tumor cells to cisplatin.…”

Treatment of recurrent and platinum-refractory stage IV non-small cell lung cancer with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as a single agent

“…Nanoparticle albumin-bound paclitaxel ( nab -paclitaxel, Abraxane ® [Celgene Corporation, Summit, NJ, USA]) is a formulation of paclitaxel which is not dissolved in Cremophor EL, reducing many of the toxicities associated with this solvent. This formulation also potentially increases the delivery of paclitaxel into tumor cells via the endogenous albumin pathways[7, 8]. …”