肺癌组织中突变型p53蛋白与肿瘤耐药蛋白表达对治疗及预后影响的研究

目的:探讨突变型p53蛋白与肿瘤耐药蛋白在肺癌组织的表达特点及其临床意义.方法:免疫组化法检测66例肺癌组织中突变型p53蛋白与各种肿瘤耐药蛋白的表达,并分析治疗及其效果和生存情况.结果:不同TNM分期(χ2＝6.22,P＝0.016)、淋巴结转移(χ2＝3.88,P＝0.045)、化疗效果(χ2＝4.78,P＝0.035)及3年生存组(χ2＝5.10,P＝0.024)的突变型p53蛋白表达均差异有统计学意义;而P-糖蛋白(P-gp)、多药耐药相关蛋白(MRP)、肺耐药相关蛋白(LRP)和谷胱甘肽-S-转移酶-π(GST-π)的表达仅对近期化疗效果产生影响,P值分别为0.035、0.018、0.041和0.021.仅突变型p53蛋白阳性组和阴性组的3年生存率、中位生存期差异有统计学意义,χ2＝5.137,P＝0.023;不同病理类型肺癌患者3年生存率、生存时间的差异也有统计学意义,χ2＝19.5,P＝0.001.结论:突变型p53蛋白的检测能在一定程度上反映肺癌的TNM分期、淋巴结转移、化疗效果和预后;而P-gp、MRP、GST-π和LRP的检测只能提示肺癌的近期化疗效果;不同病理类型的肺癌患者预后不同.     

肺癌组织中突变型p53蛋白与肿瘤耐药蛋白表达对治疗及预后影响的研究

目的：探讨突变型p53蛋白与肿瘤耐药蛋白在肺癌组织的表达特点及其临床意义。方法：免疫组化法检测66例肺癌组织中突变型p53蛋白与各种肿瘤耐药蛋白的表达，并分析治疗及其效果和生存情况。结果：不同TNM分期（χ^2 =6．22，P=0．016）、淋巴结转移（χ^2 =3．88，P=0．045）、化疗效果（χ^2 =4．78.P=0．035）及3年生存组（χ^2 =5．10，P=0．024）的突变型p53蛋白表达均差异有统计学意义；而P-糖蛋白（P-gp）、多药耐药相关蛋白（MRP）、肺耐药相关蛋白（LRP）和谷胱甘肽-S-转移酶-π（GST-π）的表达仅对近期化疗效果产生影响，P值分别为0．035、0．018、0．041和0．021。仅突变型p53蛋白阳性组和阴性组的3年生存率、中位生存期差异有统计学意义，χ^2 =5．137，P=0．023；不同病理类型肺癌患者3年生存率、生存时间的差异也有统计学意义，χ^2 =19．5，P=0．001。结论：突变型p53蛋白的检测能在一定程度上反映肺癌的TNM分期、淋巴结转移、化疗效果和预后；而P-gp、MRP、GST-π和LRP的检测只能提示肺癌的近期化疗效果；不同病理类型的肺癌患者预后不同。     

头颈鳞癌切缘突变型p53表达与肿瘤局部复发和预后的关系

目的:探讨头颈鳞癌手术切缘p53表达及其与肿瘤局部复发和预后的关系.方法:用免疫组织化学的方法检测82例头颈鳞癌患者手术切缘中p53的表达情况.并分析其与肿瘤局部复发,临床病理学参数和预后之间的关系.结果:在82例头颈鳞癌患者中,切缘突变型p53阳性表达率为59.76%(49/82).阳性表达主要定位于切缘上皮细胞核.p53蛋白在头颈鳞癌手术切缘中的表达显著高于其在正常口腔粘膜组织中的表达(x2=10.497,P＜0.05).头颈鳞癌患者手术切缘p53的表达与肿瘤分化程度(x2=12.332,P＜0.01)和局部复发显著相关(x2=5.425,P＜0.05),但与患者年龄、性别、肿瘤病理分期以及淋巴结转移无关(P＞0.05).切缘p53表达阴性组较阳性组术后可能有较好的预后(x2=3.559,P=0.059).结论:切缘p53的阳性表达与头颈鳞癌术后肿瘤的进展有关,它有望成为指导头颈鳞癌治疗和判断预后的一项重要指标.     

膀胱移行细胞癌P—gp表达与凋亡相关蛋白p53、bcl—2的关系

目的探讨膀胱移行细胞癌组织中MDR1基因产物P-gp表达与凋亡相关蛋白p53、bcl-2的相互关系及其临床意义.方法采用免疫组化S-P法检测107例原发性膀胱移行细胞癌组织中P-gp、p53、bcl-2蛋白的表达情况.结果P-gp、p53、bcl-2蛋白的阳性表达率分别为63.6%、72.9%、54.2%,三者的过度表达均与膀胱癌的病理分级、临床分期和术后腔内化疗后复发有关;P-gp表达与p53、bcl-2蛋白的表达密切相关(P＜0.01或P＜0.05).结论P-gp、p53、bcl-2蛋白的过度表达不仅是判定原发性膀胱移行细胞癌恶性程度和预后的重要指标,而且凋亡相关蛋白p53、bcl-2可能参与膀胱移行细胞癌多药耐药的形成.     

喉鳞癌原发灶和切缘p53蛋白表达及其与术后放疗的关系

目的 分析喉鳞癌原发灶和病理学阴性切缘中p53蛋白表达与术后放疗的关系。方法 回顾性分析67例喉鳞癌的临床资料,采用免疫组化方法检测病理学阴性切缘和原发灶中p53蛋白表达情况。结果 切缘和原发灶中p53阳性率分别为19．4％(13／67)和50．7％(34／67)。在原发灶p53阳性组中,与术后未放疗者相比,术后放疗者的生存率较未放疗者高(P=0．0005),复发率比较低(P=0．002);而在原发灶p53阴性组中,术后放疗者的生存率、复发率与未放疗者差异无显著性(P=0．4096,P=0．175)。在切缘p53蛋白阳性组中,术后放疗者的生存率和复发率与未放疗者差异无显著性、(P=0．378l,P=1．0);在切缘p53蛋白阴性组中,术后放疗者的生存率和复发率与未放疗者差异无显著性(P=0．0743,P=0．248)。结论 对喉鳞癌原发灶p53蛋白阳性表达者进行术后放疗是有必要的,但病理学阴性、而p53蛋白阳性切缘暂不能作为术后放疗与否的依据。     

非小细胞肺癌组织p53和c-erbB2及MRP蛋白的表达

目的探讨癌组织p53、c-erbB2、MRP蛋白表达与非小细胞肺癌（NSCLC）临床病理特征的关系及其预后评估意义。方法应用免疫组织化学方法检测NSCLC患者的肺组织切除标本p53、c-erbB2、MRP蛋白表达,并与其临床病理参数进行比较分析。结果NSCLC组织p53、c-erbB2、MRP蛋白表达阳性率分别为53.9%（82/152）、44.1%（67/152）及43.4%（66/152）。p53表达与性别、细胞分化程度、临床分期、淋巴结转移有显著关系（P〈0.05）,而c-erbB2与各因素间无统计学差异,肺腺癌MRP蛋白表达阳性率（67.6%）明显高于肺鳞癌（33.0%）,有统计学差异（P〈0.05）。癌组织p53、c-erbB2、MRP 3种蛋白表达均阳性者的1、2、3年生存率明显低于均阴性者（分别P=0.02、0.01和0.00）,p53、c-erbB2、MRP蛋白表达阳性者单纯手术后生存率也明显低于阴性者（P〈0.05）;p53、c-erbB2、MRP 3种蛋白表达均阴性者预后最好,1-2种阳性者次之,3种均阳性者预后最差（P〈0.05）。术后辅助化疗组MRP、c-erbB2蛋白表达阳性者的生存率低于阴性者（P〈0.01）,但p53蛋白表达阳性与阴性患者的生存率无统计学差异（P=0.82）;MRP与c-erbB2表达双阴性者生存率显著高于双阳性者,MRP或c-erbB2单一阳性的生存率介于前两者之间（P=0.01）。多因素Cox分析显示细胞分化程度、c-erbB2是影响NSCLC患者疗效和预后的独立预测因子。结论肿瘤组织p53、c-erbB2、MRP 3种蛋白同时高表达的NSCLC病例预后较差。术后检测p53、c-erbB2、MRP表达对评估可手术NSCLC患者疗效和预后有一定意义。     

乳腺癌组织突变型p53和抑癌基因PTEN表达及其临床意义的研究

目的：探讨乳腺癌中是否存在突变型p53的过度表达和抑癌基因PTEN的失活，及其对预后的影响。方法：SP免疫组化法检测260例乳腺癌患者中突变型p53和PTEN的表达情况。结果：乳腺癌中突变型p53阳性率44．62％（116／260），阳性患者5年生存率（52．59％）低于阴性患者（65．97％），差异有统计学意义，χ^2=4．26，P=0．039。抑癌基因PTEN的阳性率为69．23％，阳性患者5年生存率（65．00％）高于PTEN阴性患者（48．75％），差异有统计学意义，χ^2=5．44，P=0．0197。抑癌基因PTEN与突变型p53共同阳性69例，共同阴性33例，两者之间呈负相关，χ^2=25．924，P=0．0000。结论：p53基因的突变和PTEN基因的失活可能与乳腺癌发生密切相关，且均与预后相关，可作为预后评估指标之一。     

Pgp、p53与c—erbB—2蛋白在乳腺癌组织中的表达及其临床意义

目的 探讨乳腺癌组织中Pgp、p53与c-erbB-2蛋白的表达水平、相互关系及其临床意义。方法 采用免疫组织化学ABC法,检测82例手术切除乳腺癌组织中Pgp、p53及c-erbB-2蛋白的表达水平。结果 乳腺癌组织中Pgp、p53及c-erbB-2蛋白的阳性表达率分别为42.7%,13.4%和54.4%;P－gp与p53蛋白表达有显著相关性（P＜0.05）,与c-erbB-2蛋白表达无显著相关性（P＞0.05);P-gp表达在不同年龄、不同病理类型、有无淋巴结转移及临床分期之间无显著性差异;P-gp阳性组和P-gp阴性组5年无瘤生存率无显著性差异（P＞0.05）。结论 乳腺癌组织具有多药耐药性;p53蛋白表达与P-gp表达有相关关系。     

口咽鳞癌组织中人乳头状瘤病毒DNA状态与p16蛋白表达的相互关系及临床意义

目的 探讨联合检测口咽鳞癌组织标本中人乳头状瘤病毒(HPV)的感染情况与p16蛋白表达的临床意义.方法 选择66例口咽鳞癌活检或手术标本,采用“三明治”技术对组织标本进行切片,以SPF10-DNA LiPA分型方法检测HPV-DNA状态,采用免疫组织化学法检测p16蛋白的表达情况,分析不同HPV-DNA和p16蛋白表达患者的预后.结果 66例口咽鳞癌患者中,HPV-DNA阳性11例,阳性率为16.7％ (11/66).11例HPV-DNA阳性患者中,p16蛋白阳性9例,阴性2例.55例HPV-DNA阴性患者中,p16蛋白阳性12例,阴性43例.在口咽鳞癌中,HPV-DNA的表达与p16蛋白的表达具有显著的相关性(P ＜0.001).HPV-DNA和p16蛋白均为阳性组(A组)9例,HPV-DNA阳性/p16蛋白阴性或HPV-DNA阴性/p16蛋白阳性组(B组)14例,HPV-DNA和p16蛋白均为阴性组(C组)43例.A组、B组和C组患者的3年总生存率分别为100％、77.8％和42.0％,差异有统计学意义(P=0.001);3年疾病特异性生存率分别为100％、77.8％和46.4％,差异有统计学意义(P =0.004).结论 在口咽鳞癌中,HPV-DNA的表达与p16蛋白的表达具有显著的相关性,p16蛋白是较为可靠的预测HPV状态的替代标志.联合检测HPV-DNA和p16蛋白的状态,有助于更加准确地对口咽鳞癌进行分层,并判断预后.     

膀胱癌细胞凋亡、P-gP、MDM2、p53基因表达的意义

目的:研究膀胱癌细胞凋亡、P-gp、MDM2、p53基因表达的意义。方法:采用免疫组化法及TUNEL法检测11例正常膀胱黏膜和83例膀胱移行细胞癌中P-gp、MDM2、p53基因的表达及细胞凋亡指数(AI)。结果:83例膀胱移行细胞癌中P-gp阳性71.08%,p53阳性50.6%,MDM2阳性59.03%,AI=1.4335±0.3863。MDM2阳性表达与病理分级及临床分期呈负相关(r=-0.263,P=0.016及r=-0.388,P=0.001);p53阳性表达与病理分级及临床分期呈正相关(r=0.492,P=0.001;r=0.341,P<0.01);P-gp阳性表达与病理分级及临床分期无相关性;P-gp、MDM2、p53 3种蛋白间表达无相关性;AI与MDM2呈负相关(r=-0.226,P=0.042);AI与病理分级及临床分期呈正相关(r=0.642,P=0.000;r=0.455,P=0.000);AI与P-gp、p53无相关性。AI、p53、MDM2的表达与5年生存率有关。结论:检测P-gp可指导膀胱癌化疗药物的选择;联合运用临床分期及病理分级并检测p53、MDM2可用于判断膀胱移行细胞癌的预后。     

免疫电镜方法研究P-gp、p53蛋白、Bcl-2蛋白在肺癌组织中的表达

目的 从超微水平了解P－gp、p53蛋白、Bcl-2蛋白在肺癌组织中的表达，探讨它们与多药耐药（multidrug resistance,MDR)的关系和可能的作用机制。方法 8例非小细胞肺癌（NSCLC）手术标本和7例小细胞肺癌（SCLC）经支气管镜活检标本，用免疫电镜方法包埋后，以PAG标记抗体方法检测P－gp、p53蛋白、Bcl-2蛋白的表达。结果 P－gp主要位于胞膜和胞浆内质网附近；p53主要位于细胞核异染色质上，胞浆中也有存在；Bcl-2分布与线粒体和内质网有关。三者在15例肺癌中的表达率分别为33．3％（5／15）、60．0％（9／15）和26．7％（4／15）。8例手术获得的正常肺组织标本中，3种蛋白表达均为阴性。5例P－gp阳性的标本中，4例为NSCLC，仅1例为化疗后的SCLC。结论 用免疫电镜方法检测，P－gp、p53蛋白、Bcl-2蛋白在肺癌中有一定的表达。P－gp与p53、p53与Bcl-2的表达无相关性。P－gp主要位于胞膜，支持其膜上药物输出泵的功能，其表达在肺癌的MDR中起一定作用，但不是惟一因素。     

Prognostic value of the epidermal growth factor receptor (EGRF) and p53 in advanced head and neck squamous cell carcinoma patients treated with induction chemotherapy

We measured the expression of the p53 nuclear protein and epidermal growth factor receptor (EGFR) in 46 biopsy samples from patients with advanced head and neck cancer treated with induction combination chemotherapy of 5-fluorouracil, cisplatin, and paclitaxel. Tumour expression of p53 protein was analysed with the monoclonal D07 antibody and EGFR with monoclonal H11 antibody. The overall response, defined as complete (CR) and partial response (PR) rates to treatment, was 88%. p53 positive staining was significantly more frequent in patients who did not respond to the induction treatment. EGFR expression failed to show any correlation with the response rate. Multivariate analysis indicated that a tumour location in the oral cavity together with p53 expression combined with moderate-to-high EGFR staining were independent prognostic factors of a shorter disease-free survival (DFS). Location of the tumour in the oral cavity and EGFR expression had independent prognostic value for overall survival (OS). We conclude that the EGFR status and an oral cavity location of the tumour have independent prognostic value in patients with advanced head and neck carcinoma treated with induction chemotherapy. The p53 status appears to be a determinant of the tumour chemo-sensitivity in advanced head and neck squamous cell carcinoma (HNSCC). The presence in the tumour of a p53-positive stain and moderate-to-high staining of EGFR is associated with a shorter DFS and time to treatment failure (TTF) probably reflecting a more aggressive tumour phenotype.     

Pilot study examining tumor expression of RAD51 and clinical outcomes in human head cancers

Radiation therapy and chemotherapy are commonly used treatments for head and neck cancer. RAD51 is a highly conserved DNA repair protein that serves a central function in the homologous recombination pathway. High levels of RAD51 protein expression have been reported in number of human cancer cell lines, and studies suggest that RAD51 overexpression can increase cellular resistance to radiation and some chemotherapeutic drugs. In this study, RAD51 protein levels were quantified by immunohistochemistry in tumor samples from twelve head and neck cancer patients who received identical treatment with induction chemotherapy (paclitaxel and carboplatinum) followed by radiation therapy given concurrently with additional chemotherapy (paclitaxel, fluorouracil, hydroxyurea). Patients with high RAD51 protein levels in their pre-treatment tumor biopsies demonstrated poorer cancer-specific survival rates than patients with lower RAD51 levels (33.3% vs. 88.9% at 2 years; p=0.025). In addition, within a subgroup of patients with normal tumor cell p53 expression, there was a non-significant trend toward better induction chemotherapy response rates observed in the tumors with lower RAD51 protein levels. These results suggest that tumor cell RAD51 expression levels may influence the outcome of patients with head and neck cancer treated with chemotherapy and radiotherapy.     

p53 status of head and neck cancer: relation to biological characteristics and outcome of radiotherapy.

p53 status was investigated in 99 patients with squamous cell carcinoma of the head and neck region uniformly treated with accelerated radiotherapy and in whom tumour cell proliferation and DNA aneuploidy were assessed using bromodeoxyuridine (BrdUrd) incorporation and flow cytometry (FCM). Seventy-six percent of tumours were immunohistochemically positive for p53 protein, but heterogeneity was noticed both in the percentage of cells positive for p53 and in their level of expression. However, tumours which were either essentially all positive or all negative or showed sporadic positivity for p53 protein showed no differences in their level of aneuploidy, proliferation rate, tissue organisation or outcome with radiotherapy. There was a trend for those p53-positive tumours with the strongest expression to have more DNA aneuploidy and deregulation of proliferation organisation than weaker expressors; but there were no differences in proliferation rate or outcome of radiotherapy. These studies suggest that p53 protein stabilisation as assessed by immunohistochemistry does not have any major relationship with the biological characteristics and outcome of squamous cell cancer treated by accelerated radiotherapy.     

Postoperative chemotherapy vs chemoradiotherapy for thoracic esophageal cancer: a prospective randomized clinical trial.

BACKGROUND: Neither postoperative radiotherapy nor chemotherapy alone provided a survival benefit after curative esophagectomy for esophageal squamous carcinoma. MATERIAL AND METHODS: Of 103 consecutive patients who underwent potentially curative esophagectomy for esophageal squamous carcinoma, 45 patients with advanced cancers without preoperative adjuvant treatments were prospectively randomized to two groups; postoperative chemotherapy alone (Group A, n=23) and postoperative radio/chemotherapy (Group B, n=22). In Group A, cisplatin (CDDP) (50 mg/m(2)) was given by intravenous infusion on days 1 and 15, and 5-fluorouracil (5-FU) (300 mg/m(2)) was given daily by continuous intravenous infusion for 5 weeks. In Group B, in addition to the same chemotherapeutic regimen of Group A, 50 Gy of radiotherapy was given to the mediastinum over 5 weeks. The immunohistochemical staining of tumoral p53 and microvessel density was undertaken to correlate to the radio/chemosensitivity. RESULTS: There were no significant differences in the clinicopathologic characteristics between the two groups. The median dose of 5-FU and CDDP administered were not significantly different between the two groups. The mean (SD) dose of radiotherapy in Group B was 42+10 Gy. The 1-, 3- and 5-year survival rates in Group A were 100, 63 and 38% and those in Group B were 80, 58 and 50%, respectively (P=0.97). In each group, four patients succumbed to locoregional recurrences.Tumoral p53 was immunohistochemically negative in 43% in Group A and 77% in Group B (P=0.03), indicating that many patients in Group B might be potentially sensitive to radiochemotherapy. The 3- and 5-year survival rates (75 and 64%) of patients with p53 negative expression (n=18) were significantly (P=0.03) better than those with p53 positive expression (n=27, 44 and 26%). The long-term survival was better for patients with p53 negative tumours than those with p53 positive tumours in Group B (P=0.06 by long-rank test, P<0.05 by Generalized-Wilcoxon test). However, the long-term survival was not different between the patients who had p53 negative and positive tumours in Group A (P=0.19). These data suggest that there were no survival advantage for patients receiving radiotherapy in Group B, instead p53 negative tumours appeared to have a favorable prognosis. CONCLUSION: Postoperative radiotherapy administered concurrently with chemotherapy does not provide a survival benefit compared with chemotherapy alone. Tumoral p53 expression has a predictive value for survival in patients treated with postoperative radio/chemotherapy.     

Predictive value of P53, BCL-2, and BAX in advanced head and neck carcinoma

Because the apoptotic process appears to be involved in the response-to-treatment of chemotherapy and radiotherapy, we investigated the prognostic value of the expression of three apoptosis-associated genes (p53, Bax, and Bcl-2) in tumor biopsies from patients with locally advanced head and neck carcinoma. Using specific monoclonal antibodies, immunohistochemical staining for p53, Bax, and Bcl-2 was performed on tumor material from 43 patients before their scheduled adjuvant chemoradiotherapy. Results indicated that the response to treatment was 83.7% (36 of 43 patients). Bax staining was positive in 8 cases (19.5%), p53 in 19 (47.5%), and Bcl-2 in 4 patients (10.8%). There were no statistically significant correlations between any of the apoptosis genes assayed and the patients' response to treatment or to overall survival. In the univariate statistical analysis, response-to-treatment was the only significant variable (p = 0.013) predictive of survival rate. These results suggest that p53, Bax, and Bcl-2 expression are not significant predictive factors of response to induction treatment in locally advanced head and neck carcinoma and that their routine use as prognostic markers cannot be recommended.     

胰腺癌组织中Ki67、p53的表达及其与高剂量少分次放疗生存时间的关系

目的:分析Ki67、p53在胰腺癌组织中的表达水平,及其与患者接受高剂量少分次放疗生存时间的关系。方法:回顾性收集55例胰腺癌患者接受高剂量少分次放疗前的活检病理组织,采用免疫组化SP法检测Ki67及p53在胰腺癌组织中的表达水平,并采用Log-rank检验比较不同表达水平组间生存时间的差异,Cox模型行多因素分析统计。结果:Ki67、p53蛋白在穿刺组织中的表达率分别为41.8%、47.3%,单因素生存分析显示Ki67、p53阴性表达组的生存时间在统计学上明显长于阳性组（P均<0.05）,多因素分析提示Ki67、p53及远处转移均是胰腺癌患者接受高剂量少分次放疗生存时间的独立预后影响因素。结论:放疗前活检病理组织中Ki67、p53蛋白表达水平是预测胰腺癌高剂量少分次放疗生存时间的重要指标。     

头颈部恶性肿瘤P—糖蛋白的表达

目的：探讨头颈部恶性肿瘤P-糖蛋白在化疗耐药中的作用、方法：用单克隆抗体MRK16检测50例头颈部恶性肿瘤（鳞癌38例，腺癌9例，肉瘤3例）组织标本中卜糖蛋白的表达。结果：P-糖蛋白表达阳性为58％，其与化疗史和肿瘤分化程度有关，化疗后复发患者P-糖蛋白表达阳性率明显高于未化疗组（P＜0.05），高分化组P-糖蛋白表达明显高于中、低分化组（P＜0．05）。P-糖蛋白表达与临床化疗效果相对照，其预测化疗疗效准确率达75％。结论：多药耐药基因编码的P-糖蛋白在化疗失败中的作用不可忽视。首次药物治疗应采用足够剂量。     

原发性肝细胞癌p53蛋白和多药耐药相关蛋白的表达及意义

目的探讨原发性肝细胞癌中P-gp、p53蛋白的表达及相互关系。方法应用免疫组织化学S-P法检测37例原发性肝细胞癌及19例非肝癌肝组织中p53蛋白与P-gp的表达。结果37例原发性肝细胞癌P-gp及p53蛋白的表达率为81.08%和64.86%,19例非肝癌肝组织P-gp及p53蛋白的表达率为42.10%和36.84%,相对应的两者有显著性差异(P<0.05);在原发性肝细胞癌中,P-gp的表达与远处转移相关,p53蛋白的表达与原发性肝细胞癌远处转移、肝内转移以及肿瘤的Edmondson分级相关(P<0.05),而且P-gp表达与p53蛋白的表达间具有相关性(P<0.05)。结论原发性肝细胞癌的P-gp及p53蛋白的表达,对于临床上认识原发性肝细胞癌的生物学特性,选择合理的化疗用药及估计预后具有重要意义。     

Novel therapeutics for head and neck cancer

Head and neck squamous cell carcinoma is a clinically challenging disease that resulted in more than 500,000 cases worldwide in 2001. In the United States, head and neck squamous cell carcinoma has accounted for approximately 40,000 cases with 12,000 deaths reported in 2001, which makes it the fifth leading cause of cancer incidence and the sixth leading cause of cancer-related deaths. Patients with recurrent or metastatic disease have a median survival rate of approximately 6 months; and there is little evidence from randomized trials that survival advantages have been achieved over the community standard of cisplatin and infusional 5-fluorouracil combination. Despite significant improvements in diagnosis, local management, and chemotherapy of head and neck cancer, there has been no significant increase in long-term survival rates over the past 30 years. As little progress has been made, new management approaches are required. Novel biologic agents have been developed to target multiple specific regions of the cancer cell. Epidermal growth factor receptor blockers have been investigated, such as anti epidermal growth factor receptor monoclonal antibodies, tyrosine kinase inhibitors, ligand conjugates, immunoconjugates, and antisense oligonucleotides. Farnesyl transferase inhibitors are a class of compounds that inhibit a critical enzymatic step in the constitutive expression of mutated ras genes, which are present in more than 27% of oral cancers. Strategies targeting the p53 gene and protein may halt or reverse the process of tumorigenesis and metastasis as p53 mutations occur in 45 to 70% of head and neck squamous cell carcinoma patients. Continued development of these novel agents may help improve the overall response and survival rate of patients with head and neck cancer.