Prolonged survival of mice with human gastric cancer treated with an anti-c-ErbB-2 monoclonal antibody

Ohnishi, Yasuyuki; Nakamura, Hiroyuki; Yoshimura, M; Tokuda, Yutaka; Iwasawa, M; Ueyama, Yoshito; Tamaoki, Norikazu; Shimamura, Kazuo

doi:10.1038/bjc.1995.187

Cited by 29 publications

(18 citation statements)

References 17 publications

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“…The erbB2/HER2 oncogene is amplified in 25%-30% of breast cancers (Berger et al 1988;Guerin et al 1988), suggesting that these tumors may be addicted to HER2. Consistent with such dependency, breast cancer cells in culture or grown as xenografts in nude mice are preferentially growth inhibited by HER2-specific antibodies (Hudziak et al 1989;Shepard et al 1991;Ohnishi et al 1995;Tokuda et al 1996), antisense oligonucleotides (Brysch et al 1994;Colomer et al 1994) and HER2-targeted small molecule inhibitors such as lapatinib, HKI-272, and BMS-599626 (Xia et al 2002;Rabindran et al 2004;Wong et al 2006). These findings formed the basis for the treatment of patients with HER2-amplified metastatic breast cancer with the HER2 targeted antibodies, Trastuzumab/Herceptin and Pertuzumab (Hudis 2007).…”

Section: Activated Kinases: the "Achilles' Heel" Of Many Cancersmentioning

confidence: 59%

Oncogene addiction: setting the stage for molecularly targeted cancer therapy

Sharma¹,

Settleman²

2007

Genes Dev.

384

325

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In pugilistic parlance, the one-two punch is a devastating combination of blows, with the first punch setting the stage and the second delivering the knock-out. This analogy can be extended to molecularly targeted cancer therapies, with oncogene addiction serving to set the stage for tumor cell killing by a targeted therapeutic agent. While in vitro and in vivo examples abound documenting the existence of this phenomenon, the mechanistic underpinnings that govern oncogene addiction are just beginning to emerge. Our current inability to fully exploit this weakness of cancer cells stems from an incomplete understanding of oncogene addiction, which nonetheless represents one of the rare chinks in the formidable armor of cancer cells. 'Oncogene addiction': defining the termCancer is, an old adage goes, actually a hundred diseases masquerading as one. In our fight against this dreaded disease, casualties abound and successes are few and far between. Given the bewildering diversity of causality, it is gratifying to realize that painstaking investigation over the past 50 years has highlighted some common themes in the genesis and progression of cancer (Hanahan and Weinberg 2000). These commonalities offer a glimmer of hope that potential targets may exist within the cancer cell that can be exploited in combating these diseases. The first unifying theme is that cancer is caused by a handful of "rogue" corrupted cellular genes, designated oncogenes, that hijack the cell, causing it to survive indefinitely and proliferate aberrantly. The second unifying theme is that the genesis and progression of a tumor is governed by the activation of specific oncogenes and inactivation of tumor suppressor genes, and the stochastic accumulation of these genetic alterations progressively drives the evolution of cancer from a benign expansion of cells to an invasive and metastatic tumor. This is well illustrated by the example of colorectal cancer (Kinzler and Vogelstein 1996).On the face of it, this would suggest that cancer is a "moving target" that may be impossible to destroy. However, recently, a third common theme has begun to emerge that offers cause for guarded optimism. This phenomenon, referred to as "oncogene addiction," a term first coined in 2000 by Bernard Weinstein, reveals a possible "Achilles' heel" within the cancer cell that can be exploited therapeutically (Weinstein 2000(Weinstein , 2002Weinstein and Joe 2006). In its simplest embodiment, oncogene addiction refers to the curious observation that a tumor cell, despite its plethora of genetic alterations, can seemingly exhibit dependence on a single oncogenic pathway or protein for its sustained proliferation and/or survival. At first glance, the fact that a tumor cell can exhibit dependency on a single protein that contributed to the malignant phenotype at some point in its history may seem to be trivial. However, the fact that inactivating the normal counterpart of such oncogenic proteins in normal tissues is often tolerated without obvious consequence highlights the...

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Section: Activated Kinases: the "Achilles' Heel" Of Many Cancersmentioning

confidence: 59%

Oncogene addiction: setting the stage for molecularly targeted cancer therapy

Sharma¹,

Settleman²

2007

Genes Dev.

384

325

View full text Add to dashboard Cite

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“…The physical and functional interaction of p185c-neu and EGF receptor leads to the formation of a highly active, heterodimeric tyrosine kinase complex that synergistically activates cellular transformation. Anti-receptor antibodies have shown potential utility in the down-modulation of these cell surface proteins (46) and suppression of the malignant phenotype (47). p185 has been proposed to provide a useful target for serotherapy (48).…”

Section: Discussionmentioning

confidence: 99%

p185, an Immunodominant Epitope, Is an Autoantigen Mimotope

Kumar

Hinks

Maman

et al. 2011

Journal of Biological Chemistry

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An immunodominant peptide (p185(378 -394)) derived from the c-erbB2 gene product, was recognized by an anti-DNA antibody, B3, and importantly by two classical DNA-binding proteins, Tgo polymerase and Pa-UDG. These reactivities were inhibited by DNA, confirming that the peptide mimicked DNA. BALB/c mice immunized with p185(378 -394) developed significant titers of IgG anti-dsDNA antibodies. Screening of 39 human lupus sera revealed that 5% of these sera possessed reactivity toward p185(378 -394). Representative mouse and human sera with anti-p185(378 -394) reactivity bound intact p185, and this binding was inhibited by dsDNA. This is the first demonstration of a naturally occurring autoantigen mimotope. The present study identifies a potential antigenic stimulus that might trigger systemic lupus erythematosus in a subset of patients.

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“…Antibodies against erbB2/neu have been demonstrated eective for reducing the tumor burden and prolonging survival of treated animals with gastric cancers (Karameris et al, 1993;Ohnishi et al, 1995;Tokuda et al, 1996). Targeting erbB2-expressing cells with conjugated immunoliposomes containing chemotherapeutic reagents has also proven useful (Suzuki et al, 1995).…”

Section: Protein Localization By Immunohistochemistrymentioning

confidence: 99%

Tyrosine kinases and gastric cancer

et al. 2000

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Carcinoma of the stomach is one of the most prevalent cancer types in the world today. Two major forms of gastric cancer are distinguished according to their morphological and clinicopathological classi®cations (well dierentiated/intestinal type and poorly dierentiated/diuse type), characteristics that could also be attributed to the altered expression of dierent types of oncogenes or tumor suppressor genes. Signi®cant dierences exist for gastric cancer incidence comparing people of dierent ethnic origins, implicating various genetic and epigenetic factors for gastric oncogenesis. There are only a limited number of molecular markers available for gastric cancer detection and prognostic evaluation, among which are tyrosine kinases. There is convincing evidence that tyrosine kinases are involved in oncogenesis and disease progression for many human cancers. Ampli®cations of certain tyrosine kinases (cmet, k-sam and erbB2/neu) have been associated with human gastric cancer progression. Alternatively spliced transcripts and enhanced protein-expression levels for some of these tyrosine kinases are correlated with clinical outcomes for gastric cancer patients. With advent of high throughput techniques, it is now possible to detect nearly all expressed tyrosine kinases in a single screen. This increases the chance to identify additional tyrosine kinases as predictive markers for gastric cancers. In this article, we will ®rst review the literature data concerning certain tyrosine kinases implicated in gastric carcinogenesis and then summarize more recent work which provide comprehensive tyrosine kinase pro®les for gastric cancer specimens and cell lines. Two new gastric cancer molecular markers (tie-1 and mkk4) have been identi®ed through the use of these pro®les and demonstrated eective as clinical prognostic indicators. Oncogene (2000) 19, 5680 ± 5689.

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Prolonged survival of mice with human gastric cancer treated with an anti-c-ErbB-2 monoclonal antibody

Cited by 29 publications

References 17 publications

Oncogene addiction: setting the stage for molecularly targeted cancer therapy

Oncogene addiction: setting the stage for molecularly targeted cancer therapy

p185, an Immunodominant Epitope, Is an Autoantigen Mimotope

Tyrosine kinases and gastric cancer

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