Effective Dates: February, 2008 to February 28, 2009

WELCOME
The advent of targeted therapies heralded the integration of molecular biology with clinical medicine. While many receptors have been targeted for drug development, research has now focused on intracellular mechanisms that are necessary for cancer cell growth, proliferation, survival, and metastasis. Much attention has fallen on the mammalian target of rapamycin (mTOR), an important regulator of cell growth, survival, and motility.¹ In this 2-part newsletter series, Combination Therapy With mTOR Inhibitors: Future Directions and Strategic Therapeutic Approaches, we are examining the role of mTOR inhibition in current cancer treatment and future combination regimens.

Combinations of targeted agents and mTOR inhibition were discussed in our first newsletter, Single-Agent Efficacy and Evolving Role With Other Targeted Therapies. In this, the second half of the series, we will review the role of pathways involving mTOR in tumorigenesis, and examine the mTOR relationship to pathways involved in resistance to endocrine therapies and cytotoxic chemotherapies. Combinations of these agents with mTOR inhibitors in neuroendocrine tumors, breast cancer, and lung cancer will also be discussed.

The use of therapeutic combinations highlights the shift in cancer treatment from an individual pathway-based strategy to a system-based biologic approach. As combination regimens are increasingly investigated and approved, understanding the rationale behind their use will be of utmost importance in improving outcomes and individualizing patient care. 

Sincerely,
James C. Yao, MD
Editor