In breast cancer, nuclear p44 promotes tumor cell proliferation in an estrogen-dependent fashion. Although our siRNA-mediated knockdown experiments demonstrated that our p44 antibody specifically recognized a single protein species in prostate, breast, and ovary, we can’t completely exclude the possibility that highly related but functionally distinct proteins act as distinct hormone receptor cofactors in each of these tissues. With this caveat, our findings suggest that p44 may also act through an ER-mediated functional pathway in ovarian tissue. Neoadjuvant chemotherapy, which is the use of systemic chemotherapy before definitive surgery and/or radiotherapy, has been an attractive approach in the management of HNSCC for the last 25 years. The benefits of chemotherapy for patients with advanced HNSCC, as demonstrated by many clinical studies, include a reduction in the distant metastasis, improved long-survival, and the preservation of organ function. Unfortunately, some studies have failed to demonstrate any significant improvement in long-survival after neoadjuvant chemotherapy. Recently, Glynne-Jones et al. stated that there was no benefit in overall survival from cisplatin-based chemotherapy before radiotherapy and considered that neoadjuvant chemotherapy might be the sole effective preoperative management strategy in HNSCC. However, some studies have also shown that patients whose disease responded to neoadjuvant chemotherapy had a better survival rate in comparison those who did not receive chemotherapy or who received non-effective chemotherapy. Furthermore, it has been shown that neoadjuvant chemotherapy can increase the effectiveness of radiotherapy. Thus, neoadjuvant chemotherapy has become an area of intense study in HNSCC management; however, the original, empiricbased treatment strategies that have been historically used have resulted in many patients with chemotherapy-resistant disease, such that these patients frequently received multiple cycles of toxic therapy without success before the apparent lack of kinase inhibitors efficacy was identified. It is believed that the extreme biological heterogeneity that defines the chemotherapy-resistant phenotype and prognosis differs among patients and generally involves many factors. Accumulating evidence indicates that a high expression of cyclin D1, which is a key regulator of the G1 phase of the cell cycle, is associated with chemotherapy resistance and a poor prognosis in some solid malignant tumors. Our previous studies have also found that a high expression of CCND1 in HNSCC was closely associated with cisplatin resistance in vitro and in vivo. These results have led us to hypothesize that CCND1 could be an important target for chemotherapy response and monitoring prognosis in patients with locally advanced HNSCC. In the present study, we developed a predictive assay that is capable of selecting patients who would receive the largest possible benefit from cisplatin-based chemotherapy before surgery and post-operative radiotherapy. As a proof of principle, we investigated the direct link between CCND1 protein expression and the treatment efficacy in patients with locally advanced HNSCC.