Chemotherapy, chemoresistance and the changing treatment landscape for NSCLC.

Management of patients with lung cancer continues to pose a considerable challenge to today's oncologist. While treatment may be curative in the early stages of the disease, the majority of patients are not diagnosed until the tumor has progressed beyond the primary site. Most patients face an intensive and invasive treatment regimen comprising surgery, radiotherapy, or chemotherapy, or combinations thereof depending on disease stage/performance status. Most will require chemotherapy even if their initial surgery is potentially curative; for those with advanced disease, chemotherapy may be their only treatment option. Moreover, the majority of patients will require multiple lines of therapy as their cancer cells acquire resistance to the chemotherapeutic agents to which they are exposed. Resistance to current chemotherapeutics available for the management of non-small cell lung cancer (NSCLC) represents one of the most significant barriers to improving long-term outcomes for this vulnerable patient group. Future management may lie in individualizing therapy through careful selection of appropriate agents based on the likelihood of response and the development of resistance. A number of biomarkers are emerging that predict response to current therapeutics; work is ongoing to develop appropriate algorithms based on such markers to guide treatment selection. In addition, novel chemotherapeutics are in development including new platinum analogs such as picoplatin (a cisplatin analog), ABT-751 (a sulfonamide) and tubulin binding agents (TBAs) such as the epothilones, providing hope for the future.