Development of targeted therapy for squamous cell carcinomas of the head and neck.

Targeted therapy is a very exciting era in the treatment of squamous cell carcinomas of the head and neck. After adding cetuximab to conventional chemotherapy and radiation therapy, we are strongly considering the role of induction chemotherapy with the addition of docetaxel. At the same time, other new treatments, especially targeted agents and novel combined regimens, are being evaluated in ongoing clinical trials. For example, several trials are attempting to combine docetaxel and cetuximab in chemoradiation or induction settings. However, in the near future we are likely to see a strong presence of targeted agents that have been found to be not only effective, but also less toxic than conventional chemotherapeutic agents. Their toxicity profiles make them eligible for addition to radiation treatment strategies, as well as other chemotherapy agents, or even for replacing these chemotherapy agents. In this article, we are going to review the indications and current role of cetuximab, tyrosine kinase inhibitors (gefitinib and erlotinib), dual inhibitors, IGF receptor inhibitors, as well as other agents that are in development for treatment of head and neck squamous cell carcinomas.

Associations of MHC ancestral haplotypes with resistance/susceptibility to AIDS disease development.

We tested the association of MHC ancestral haplotypes with rapid or slow progression to AIDS by comparing their frequencies in the French genetics of resistance/susceptibility to immunodeficiency virus cohort with that reported in a control French population. Seven ancestral haplotypes were identified in the genetics of resistance/susceptibility to immunodeficiency virus cohort with a frequency >1%. The 8.1 (odds ratio (OR) = 3, p = 0.006), 35.1 (OR = 5.7, p = 0.001), and 44.2 (OR = 3.4, p = 0.007) ancestral haplotypes were associated with rapid progression, whereas the 35.2 (OR = 3.6, p = 0.001), 44.1 (OR = 5.4, p < 10(-4)), and 57.1 (OR = 5.8, p < 10(-4)) ancestral haplotypes were associated with slow progression to AIDS. Although the frequency of each ancestral haplotype is low in the population, the OR were quite higher than those previously obtained for single HLA allele associations, with some p values as low as 10(-4). The analysis of the recombinant fragments of these haplotypes allowed the identification of the MHC regions in the 35.1, 35.2, and 44.2 haplotypes associated with rapid progression to AIDS and the MHC regions of the 44.1 and 57.1 haplotypes associated with slow progression to AIDS. Previous studies have identified single HLA alleles associated with disease progression. Our results on recombinant fragments confirm the direct role of HLA-B35 in rapid progression. Associations with HLA-A29 and -B57 might be due to linkage disequilibrium with other causative genes within the MHC region.