Changhu Chen, MD, PhD

Locoregional recurrences are a major source of morbidity and mortality for patients with squamous cell carcinomas of the head and neck (HNSCC).

The treatment of head and neck cancer has been at the forefront ofnovel therapeutic paradigms. The introduction of drugs that interactwith selective biologic pathways in the cancer cell has generated considerableattention recently. A wide variety of new compounds that attemptto target growth-signaling pathways have been introduced intothe clinic. A majority of studies in the clinic have focused on epidermalgrowth factor receptor (EGFR) antagonists, but future studies will likelybuild upon or complement this strategy with agents that target angiogenicor cell-cycle pathways. EGFR activation promotes a multitude ofimportant signaling pathways associated with cancer development andprogression, and importantly, resistance to radiation. Since radiationtherapy plays an integral role in managing head and neck squamouscell cancer (HNSCC), inhibiting the EGFR pathway might improveour efforts at cancer cure. The challenge now is to understand whenthe application of these EGFR inhibitors is relevant to an individualpatient and how or when these drugs should be combined with radiationor chemotherapy. Are there molecular markers available to determinewho will respond to EGFR inhibitors and who should be treatedwith alternative approaches? What are the mechanisms behind intrinsicor acquired resistance to targeted agents, and how do we preventthis problem? We need to formulate integrated laboratory/clinicalresearch programs that address these important issues.

It is well known that the prognosisfor patients with brain metastasesfrom small cell lung cancer(SCLC) is very poor, with mediansurvivals in the range of 3 to 14months.[1-3] As pointed out by Quanet al, brain metastasis is an importantissue, given that approximately 60%of SCLC patients will develop brainmetastases sometime in the course oftheir disease. Quan et al set out towrite an article on the treatment ofbrain metastases from SCLC, but theyoften have to refer to the results ofstudies of brain metastases from othersites. Unfortunately, many studiesspecifically exclude SCLC-relatedbrain metastases, and therefore,advances in their treatment havebeen few.