p53 and HER2/neu Expression in Relation to Chemotherapy Response in Patients with Non-Small Cell Lung Cancer

Fijołek, Justyna; Wiatr, Elżbieta; Rowińska-Zakrzewska, E; Giedronowicz, Dorota; Langfort, Renata; Chabowski, Mariusz; Orłowski, T; Roszkowski, K.

doi:10.1177/172460080602100203

Cited by 26 publications

(13 citation statements)

References 30 publications

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“…P53 IHC positivity was associated with a lower probability of response71, 173, 194, 195, 400, 401, 406, with a trend towards a lower response rate397, or with significantly shorter survival71, 194, 195, 329, 401, 402 for some studies combining a platinum with a vinca alkaloid173, 329, 401, a taxane329, etoposide71, 401, gemcitabine71, 329, ifosfamide401, mitomycin-C/ifosfamide71, mitomycin-C/vindesine400, 5FU/folinic acid401, a vinca alkaloid plus radiotherapy (with or without a platinum)195, or unspecified platinum combinations194, 406. In one study in which an association was noted between p53 IHC expression and shorter overall survival, no significant association was seen with progression-free survival329.…”

Section: 0 Reduced Apoptotic Response (Fig 5)mentioning

confidence: 92%

“…NSCLC studies assessing p53 IHC positivity have included patients receiving neoadjuvant therapy397, 398 and therapy for locally advanced195, 274, 399, 400 or metastatic71, 173, 194, 214, 327, 329, 391, 401–406 disease. P53 IHC positivity was associated with a lower probability of response71, 173, 194, 195, 400, 401, 406, with a trend towards a lower response rate397, or with significantly shorter survival71, 194, 195, 329, 401, 402 for some studies combining a platinum with a vinca alkaloid173, 329, 401, a taxane329, etoposide71, 401, gemcitabine71, 329, ifosfamide401, mitomycin-C/ifosfamide71, mitomycin-C/vindesine400, 5FU/folinic acid401, a vinca alkaloid plus radiotherapy (with or without a platinum)195, or unspecified platinum combinations194, 406.…”

Section: 0 Reduced Apoptotic Response (Fig 5)mentioning

confidence: 99%

“…Similarly, Her-2/neu IHC expression did not correlate significantly with response to induction or neoadjuvant chemotherapy195, 397, 399, 532, 533 or with survival195, 399, 532, 533 in patients with stage II397 or III195, 397, 399, 532, 533 NSCLC treated with a vinca alkaloid +/− cisplatin plus radiation195, 399, neoadjuvant cisplatin-vinorelbine397 or neoadjuvant cisplatin plus etoposide (followed by postoperative radiotherapy plus either cisplatin, etoposide532 or carboplatin, vindesine533). However, there was a nonsignificant trend towards chemoresistance in tumors that were Her-2/neu positive in two studies397, 533, and in one of these two studies, chemoresistance was observed statistically significantly more often when one or both of Her-2/neu and p53 were positive397. There was also a trend to a higher proportion of tumors being positive after therapy vs pre therapy in one study, suggesting induction of Her-2/neu expression or else selection of positive tumor cells533.…”

Section: 0 Apoptosis Inhibitorsmentioning

confidence: 99%

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Tumor and host factors that may limit efficacy of chemotherapy in non-small cell and small cell lung cancer

Stewart

2010

Critical Reviews in Oncology/Hematology

161

157

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While chemotherapy provides useful palliation, advanced lung cancer remains incurable since those tumors that are initially sensitive to therapy rapidly develop acquired resistance. Resistance may arise from impaired drug delivery, extracellular factors, decreased drug uptake into tumor cells, increased drug efflux, drug inactivation by detoxifying factors, decreased drug activation or binding to target, altered target, increased damage repair, tolerance of damage, decreased proapoptotic factors, increased antiapoptotic factors, or altered cell cycling or transcription factors. Factors for which there is now substantial clinical evidence of a link to small cell lung cancer (SCLC) resistance to chemotherapy include MRP (for platinum-based combination chemotherapy) and MDR1/P-gp (for non-platinum agents). SPECT MIBI and Tc-TF scanning appears to predict chemotherapy benefit in SCLC. In non-small cell lung cancer (NSCLC), the strongest clinical evidence is for taxane resistance with elevated expression or mutation of class III β-tubulin (and possibly α tubulin), platinum resistance and expression of ERCC1 or BCRP, gemcitabine resistance and RRM1 expression, and resistance to several agents and COX-2 expression (although COX-2 inhibitors have had minimal impact on drug efficacy clinically). Tumors expressing high BRCA1 may have increased resistance to platinums but increased sensitivity to taxanes. Limited early clinical data suggest that chemotherapy resistance in NSCLC may also be increased with decreased expression of cyclin B1 or of Eg5, or with increased expression of ICAM, matrilysin, osteopontin, DDH, survivin, PCDGF, caveolin-1, p21WAF1/CIP1, or 14-3-3sigma, and that IGF-1R inhibitors may increase efficacy of chemotherapy, particularly in squamous cell carcinomas. Equivocal data (with some positive studies but other negative studies) suggest that NSCLC tumors with some EGFR mutations may have increased sensitivity to chemotherapy, while K-ras mutations and expression of GST-pi, RB or p27kip1 may possibly confer resistance. While limited clinical data suggest that p53 mutations are associated with resistance to platinum-based therapies in NSCLC, data on p53 IHC positivity are equivocal. To date, resistance-modulating strategies have generally not proven clinically useful in lung cancer, although small randomized trials suggest a modest benefit of verapamil and related agents in NSCLC.

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Section: 0 Reduced Apoptotic Response (Fig 5)mentioning

confidence: 92%

Section: 0 Reduced Apoptotic Response (Fig 5)mentioning

confidence: 99%

Section: 0 Apoptosis Inhibitorsmentioning

confidence: 99%

See 1 more Smart Citation

Tumor and host factors that may limit efficacy of chemotherapy in non-small cell and small cell lung cancer

Stewart

2010

Critical Reviews in Oncology/Hematology

161

157

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“…48 For instance, the overexpression of v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (ERBB2), which is common in breast and ovarian carcinomas, 189, 190 has been suggested to promote CDDP resistance not only by delivering robust pro-survival signals via the v-akt murine thymoma viral oncogene homolog 1 (AKT1) signaling axis, but also by finely regulating the transitory cell cycle arrest that is required for the repair of CDDP-induced DNA lesions. 191, 192 Along similar lines, dual-specificity Y-phosphorylation-regulated kinase 1B (DYRK1B, also known as MIRK) appears to sustain CDDP resistance as it favors the expression of various antioxidant enzymes. 193 By augmenting the intracellular pool of antioxidants, DYRK1B may actually reduce the susceptibility of cancer cells to CDDP via on-target, post-target as well as off-target mechanisms.…”

Section: Mechanisms Of Resistancementioning

confidence: 99%

Systems biology of cisplatin resistance: past, present and future

Vitale²,

et al. 2014

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The platinum derivative cis-diamminedichloroplatinum(II), best known as cisplatin, is currently employed for the clinical management of patients affected by testicular, ovarian, head and neck, colorectal, bladder and lung cancers. For a long time, the antineoplastic effects of cisplatin have been fully ascribed to its ability to generate unrepairable DNA lesions, hence inducing either a permanent proliferative arrest known as cellular senescence or the mitochondrial pathway of apoptosis. Accumulating evidence now suggests that the cytostatic and cytotoxic activity of cisplatin involves both a nuclear and a cytoplasmic component. Despite the unresolved issues regarding its mechanism of action, the administration of cisplatin is generally associated with high rates of clinical responses. However, in the vast majority of cases, malignant cells exposed to cisplatin activate a multipronged adaptive response that renders them less susceptible to the antiproliferative and cytotoxic effects of the drug, and eventually resume proliferation. Thus, a large fraction of cisplatin-treated patients is destined to experience therapeutic failure and tumor recurrence. Throughout the last four decades great efforts have been devoted to the characterization of the molecular mechanisms whereby neoplastic cells progressively lose their sensitivity to cisplatin. The advent of high-content and high-throughput screening technologies has accelerated the discovery of cell-intrinsic and cell-extrinsic pathways that may be targeted to prevent or reverse cisplatin resistance in cancer patients. Still, the multifactorial and redundant nature of this phenomenon poses a significant barrier against the identification of effective chemosensitization strategies. Here, we discuss recent systems biology studies aimed at deconvoluting the complex circuitries that underpin cisplatin resistance, and how their findings might drive the development of rational approaches to tackle this clinically relevant problem.

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“…For instance, the Akt-related pathway is one of the main factors that may intervene in the development of increased resistance to cis-diamminedichloroplatinum (II) therapy [141, 158, 159]. The anticancer compound cis-diamminedichloroplatinum (II) is more commonly known either as cisplatin or CDDP [141, 158, 159, 161] and has been utilized for the treatment of several types of solid tumors, such as ovarian, testicular, head and neck, lung, colorectal, and bladder cancers [141, 160–164]. Cisplatin-mediated suppression of tumor growth occurs through various types of mechanisms [141].…”

Section: Abnormal Akt-related Pathways In Resistance To Cancer Thementioning

confidence: 99%

The Role of the Dysfunctional Akt-Related Pathway in Cancer: Establishment and Maintenance of a Malignant Cell Phenotype, Resistance to Therapy, and Future Strategies for Drug Development

Romano

2013

Scientifica

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Akt serine/threonine kinases, or PKB, are key players in the regulation of a wide variety of cellular activities, such as growth, proliferation, protection from apoptotic injuries, control of DNA damage responses and genome stability, metabolism, migration, and angiogenesis. The Akt-related pathway responds to the stimulation mediated by growth factors, cytokines, hormones, and several nutrients. Akt is present in three isoforms: Akt1, Akt2, and Akt3, which may be alternatively named PKBα, PKBβ, and PKBγ, respectively. The Akt isoforms are encoded on three diverse chromosomes and their biological functions are predominantly distinct. Deregulations in the Akt-related pathway were observed in many human maladies, including cancer, cardiopathies, neurological diseases, and type-2 diabetes. This review discusses the significance of the abnormal activities of the Akt axis in promoting and sustaining malignancies, along with the development of tumor cell populations that exhibit enhanced resistance to chemo- and/or radiotherapy. This occurrence may be responsible for the relapse of the disease, which is unfortunately very often related to fatal consequences in patients.

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p53 and HER2/neu Expression in Relation to Chemotherapy Response in Patients with Non-Small Cell Lung Cancer

Cited by 26 publications

References 30 publications

Tumor and host factors that may limit efficacy of chemotherapy in non-small cell and small cell lung cancer

Tumor and host factors that may limit efficacy of chemotherapy in non-small cell and small cell lung cancer

Systems biology of cisplatin resistance: past, present and future

The Role of the Dysfunctional Akt-Related Pathway in Cancer: Establishment and Maintenance of a Malignant Cell Phenotype, Resistance to Therapy, and Future Strategies for Drug Development

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