HNSCC

Khuri FRL, Lee JJ, Winn RJ. Interim Analysis of Randomized Chemoprevention Trial of HNSCC. Proc Annu Meet Am Soc Clin Oncol 1999 18 A 1503. 

Brun et at. [96] assessed the value of [ F]-FDG-PET in prediction of therapy outcome in 47 patients with locally advanced head and neck squamous cell carcinoma (HNSCC). As early as 5-10 days after initiation of radiotherapy, determination of the metabolic rate was correlated with 5-year survival. Patients with a metabolic rate lower than the median turned out to have a significantly higher 5-year survival (72% vs. 35%, p = 0.004), whereas determination of SUV showed no correlation at this time point. 

Kothari V et al (2010) HD AC inhibitor valproic acid enhances tumor cell kill in adenovirus-HSVtk mediated suicide gene therapy in HNSCC xenograft mouse model. Int J Cancer 126 (3) 733-742... 

B13 Acid ceramidase inhibitor Prostate, Colon and HNSCC... 

Pyridinium ceramide Mitochondrial targeting HNSCC, lung, colon and breast... 

D-MAPP, D-eryt/iro-2-(N-myristoylamino)-l-phenyl-l-propanol HNSCC, Head and neck... 

Thus, taken together, these studies indicate that therapeutic strategies that induce tumor levels of ceramide, particularly Cig-ceramide in HNSCC, while decreasing SIP accumulation in the serum would be ideal for improving the therapeutic outcome of some cancers in the clinic (Fig. 16.4). 

Fig. 16.4 Roles of ceramide and SIP in anti-cancer therapeutics. The cellular balance between ceramide in tumor samples and SIP is believed to determine the fate of cancer cells. Often, within a tumor, there are altered levels/accumulation of ceramide (such as low Cig-ceramide levels in HNSCC) and high SIP levels, which are often secreted into the serum at relatively high concentrations. This causes the metabolic balance to favor SIP resulting in a pro-survival outcome. However, new therapies are being explored to shift this balance in favor of ceramide. Ultimately, these new treatments are aimed at increasing ceramide levels while inhibiting SIP generation, secretion, or signaling through SlPRs...

Karahatay, S., Thomas, K., Koybasi, S., Senkal, C.E., Elojeimy, S., Liu, X., Bielawski, J., Day, T.A., Gillespie, M.B., Sinha, D., Norris, J.S., Hannun, Y.A., and Ogretmen, B. Clinical relevance of ceramide metabolism in the pathogenesis of human head and neck squamous cell carcinoma (HNSCC) attenuation of C(18)-ceramide in HNSCC tumors correlates with lymphovascular invasion and nodal metastasis. Cancer Lett, 256, 2007, 101-111. 

CP carboplatin-paclitaxel 5-FU 5-fluorouracil HNSCC head and neck squamous cell carcinoma IFL irinotecan, 5-fluorouraciI, leucovorin N number of patients NR not reported CRC colorectal cancer NSCLC nonsmall cell lung cancer OS overall survival PFS progression-free survival RR response rate RT radiotherapy. 

Cetuximab is also FDA approved for the treatment of locally advanced and metastatic head and neck squamous cell carcinoma (HNSCC). In a phase III trial, patients with locally advanced HNSCC were randomized to radiation therapy with or without cetuximab. The addition of cetuximab provided a... 

Giannini, R, Maestro, R., Vukosa, T., Vljevic, T., Pomponi, R, and Boiocchi, M. 1997. All-TRANS, 13-CIS and 9-CIS retinoic acids induce a fully reversible growth inhibition in HNSCC cell lines Implications for in vivo retinoic acid use. Int. J. Cancer 70 194—200. 

Joo, N.E., Ritchie, K., Kamarajan, P., Miao, D., Kapila, Y.L., 2012. Nisin, an apoptogenic bacteriocin and food preservative, attenuates HNSCC mmorigenesis via CHACl. Cancer Medicine 1, 295—305. 

Tumor overexpression E.g., HNSCC, breast cancer E.g., neuroblastomas, SCLC ... 

HNSCC head and neck small cell cancer, SCLC small cell lung cancer... 

Eriksen JG et al. (2005a) The possible role of TP53 mutation status in the treatment of squamous cell carcinomas of the head and neck (HNSCC) with radiotherapy with different overall treatment times. Radiother Oncol 76(2) 135-142 Eriksen JG, Steiniche T, Overgaard J (2005b) The influence of epidermal growth factor receptor and tumor differentiation on the response to accelerated radiotherapy of squamous cell carcinomas of the head and neck in the randomized DAHANCA 6 and 7 study. Radiother Oncol 74(2) 93-100... 

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