Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Targeted Therapy”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources
PubMed2005

Emerging targeted therapies for breast cancer.

Targeted therapies offer a new approach to breast cancer treatment. Rather than eliminating both malignant and normal cells nonspecifically, these so-called "rational" therapies exploit second messenger proteins, ligands, and receptors that are known to be upregulated in neoplastic cells, or are implicated in cancer metastasis. This review will highlight a number of these targets and the mechanisms that have been targeted in drug design. We will also describe recently completed and currently ongoing clinical trials investigating targeted therapies and their potential to augment standard breast cancer therapy.

Antibodies, Monoclonal↗
PubMed1994

[Progress in targeting therapy for hepatic cancer].

Targeting therapy for hepatic cancer is divided into a method using Lipiodol as drug carrier and a method employing immunological responses of monoclonal antibodies to the tumor antigens. For the latter method, immuno-conjugates of antibodies and cytotoxic agents have been studied. Because of the lower response rates of conventional chemotherapy. Lipiodol as drug carrier provides the most effective targeting therapy on hepatic cancer at the present time. Immunotherapy using cytotoxic cells, however, did not result in sufficient clinical efficacy on the liver cancer. The system for accumulation of the effective and sufficient number of cytotoxic cells or immunoconjugates in the targeting tumor tissues are expected to be investigated.

Antibodies, Monoclonal↗
PubMed2005

Targeted therapies for gynecologic malignancies.

Despite the enormous promise that targeted therapies hold for patients with gynecologic malignancies, it is far too early to recommend any targeted therapy outside of a clinical trial. There remains considerable work to be done before targeted therapies will have a significant role in this patient population. We have learned that different tumor types express different targets, but that the mere expression of a target does not necessarily correlate with benefit from the use of the targeted agent. No less important is the challenge of determining how these agents should be studied in clinical trials, and what constitutes an active agent. To document efficacy, targeted agents would hopefully produce response (ie, shrinkage of measurable tumor), but as cytostatic agents, the ability to delay tumor growth or slow the development of symptoms would be clinically important. Combining targeted therapies with cytotoxic agents, radiation, or other targeted therapies may be important areas for study, but it is essential to demonstrate the additive or synergistic effect of the targeted therapy to an already established active one. This review covers strategies used to develop targeted agents, reviews available targeted therapies, and suggests potential roles in the treatment of gynecologic cancers.

Combined Modality Therapy↗
PubMed2006

CDC4 gene expression as potential biomarker for targeted therapy in prostate cancer.

Targeted therapy of proteasome regulated gene expression has potential utility in cancer treatment since components of ubiquitin-mediated proteolysis are altered in human malignancy. Specific regulators of proteasome degradation such as F-box proteins of the SCF E3 ligase complex are ideal biomarkers for assessing therapeutic efficacy since these components determine substrate specificity. An F-box protein that appears to be important in this process is human Cdc4 (Fbw7) since expression is detected in a variety of human cancers including breast, colon, pancreas and uterus. The role of Cdc4 in tumorigenesis appears to be related at least in part to regulation of cyclin E since inactivating mutations of CDC4 in cancer cells leads to cyclin E overexpression and genomic instability. In order to investigate the potential biological and clinical consequences of proteasome inhibition with respect to Cdc4 mediated targeted proteolysis, we investigated CDC4 expression and genetic alterations in 53 primary human prostate cancers in addition to correlation with relevant histopathological and clinical parameters. We identified genetic alterations in 6% of our prostate cancers while differential expression of Cdc4 isoforms correlated with advanced pathological stage and clinical recurrence. Our data suggest that CDC4 expression in prostate cancer has important biological and clinical implications since genetic alterations, differential Cdc4 isoform expression, histopathological and clinical correlation were demonstrated in our analysis. Therefore molecular genetic analysis of CDC4 expression may be an important biomarker for concurrent or subsequent clinical investigation of proteasome targeted therapy in men with prostate cancer.

Antineoplastic Agents↗
PubMed2005

Differentiation and definition of vascular-targeted therapies.

The therapeutic potential of targeting the tumor vascular supply is now widely recognized. Intense research and development activity has resulted in a variety of investigational agents, a number of which are currently in clinical development. As these novel agents are quite distinct from the cytotoxic drugs conventionally used in the treatment of solid tumors, it will be particularly important to ensure early differentiation of these vascular-targeted therapies in order to encourage widespread understanding of their potential benefits and application in the clinic. Two distinct groups of vascular-targeted therapies have evolved: antiangiogenic agents and vascular-disrupting approaches. These differ in three key respects: their physiologic target, the type or extent of disease that is likely to be susceptible, and the treatment scheduling. Inhibitors of angiogenesis interfere with new vessel formation and therefore have a preventative action, require chronic administration, and are likely to be of particular benefit in early-stage or asymptomatic metastatic disease. Vascular-disrupting agents target the established tumor blood vessels, resulting in tumor ischemia and necrosis. These agents are therefore given acutely, show more immediate effects, and may have particular efficacy against advanced disease. It is essential that these agents can be readily distinguished from conventional therapies and that an understanding of key differences between the two types of vascular-targeted therapies is fostered. Here, a simple taxonomy and nomenclature is proposed in anticipation that the therapeutic potential of this novel class can be realized as these approaches advance in clinical settings and a new anticancer strategy becomes available in the clinic.

Angiogenesis Inhibitors↗
PubMed2005

Molecularly targeted therapies for breast cancer.

BACKGROUND: The management of patients with localized and advanced breast cancer continues to evolve. Chemotherapy, endocrine therapy, and trastuzumab are effective therapies but leave considerable room for improvement. As the cellular aberrations inherent to cancer cells in general and breast cancer cells specifically are better understood, therapies to target specific cellular pathways continue to be developed with the goal of expanding available effective therapy through better patient selection. METHODS: We conducted a computerized search of the medical literature as well as a manual search of selected meeting abstracts. RESULTS: Several targeted therapies are in phase III clinical trials testing their promise in the treatment of breast cancer. Many other agents are completing phase I and II testing. An overview of the most promising agents in clinical development is discussed herein. CONCLUSIONS: Targeted therapy for breast cancer is a reality at this time, and several new agents hold promise for expanding and refining the pool of patients likely to further benefit from this approach in the near future.

Antibodies, Monoclonal↗
PubMedDate not supplied

Laboratory testing for HER2/neu in breast carcinoma: an evolving strategy to predict response to targeted therapy.

BACKGROUND: Laboratory testing of HER2/neu in breast carcinoma has become vital to patient care following the approval of trastuzumab as the first therapy to target the HER2/neu oncoprotein. Initial clinical trials used immunohistochemistry (IHC) to test for HER2/neu overexpression in order to select patients for therapy. Fluorescence in situ hybridization (FISH), which tests for gene amplification, is more specific and sensitive than IHC when either assay is compared with HER2/neu overexpression as determined by Northern or Western blot analysis. Many weak overexpressors on IHC testing are not gene amplified on FISH analysis. Such weak overexpressors may be considered false-positives and raise the question of how best to test for HER2/neu. METHODS: The literature was surveyed regarding testing for HER2/neu overexpression in breast carcinomas and alternative testing strategies. RESULTS: False-positive results are a significant problem when IHC is exclusively used to test for HER2/neu overexpression. The false-positives are overwhelmingly confined to the group of 2+ positives and do not respond to targeted therapy. In contrast, concordance between IHC and FISH is high when immunostaining is interpreted as either negative or strongly positive (3+). Whereas some recent studies have suggested that FISH may better predict response to anti-HER2/neu therapy than IHC, others have indicated that IHC is as effective a predictor as FISH. IHC is less technically demanding and costly than FISH. CONCLUSIONS: IHC analysis of HER2/neu in breast carcinoma is a useful predictor of response to therapy with trastuzumab when strongly positive. Negative immunostaining is highly concordant with a lack of gene amplification by FISH. Most weakly positive overexpressors are false-positives on testing with FISH. Thus, screening of breast carcinomas with IHC and confirmation of weakly positive IHC results by FISH is an effective evolving strategy for testing HER2/neu as a predictor of response to targeted therapy.

Antibodies, Monoclonal↗
PubMed2003

Biologic therapy for psoriasis: the T-cell-targeted therapies efalizumab and alefacept.

During the past several years, a new generation of therapies for psoriasis has been in development. These biologic therapies target the activity of T lymphocytes and cytokines responsible for the inflammatory nature of this disease. The first article of this 2-part update reviewed the tumor necrosis factor (TNF) inhibitors, infliximab and etanercept. In this article, we will review 2 therapies that target the T cell, efalizumab and alefacept.

Alefacept↗
PubMed2006

[Targeted therapies of cancer: not lost in translation].

The term "targeted therapies" designs treatments directed towards molecular targets present on or within tumor cells, and contributing to the process of malignant transformation. These can be categorized in several different groups: 1) Targeted therapies directed against molecular targets which play the initial and critical role in neoplastic transformation; these treatment generally yield high response rates as single agent treatment. 2) Targeted therapies on late molecular targets contributing to tumor progression, but which do not correspond to the initial event; these treatments provide limited response rates as single agent but most often improve progression free and/or overall survival in combination with cytotoxic treatments. When the molecular target is present in tumor cells, but does not contribute to neoplastic transformation, these agents are generally non active in an in vivo setting. These observations point out the need to introduce translational research as a key element to schedule and evaluate the activity of novel targeted agents in the clinics.

Antineoplastic Agents↗
PubMed2026

Targeted Therapy in Acute Myeloid Leukemia: Current Approaches and Novel Directions.

Acute myeloid leukemia (AML) is a molecularly heterogeneous neoplasm of hematopoietic stem and progenitor cells. The advent of high-resolution genomic sequencing has uncovered several genetic drivers of AML which spurred a surge of therapies that target the disease at a mutational, clonal, or epigenetic level. Currently, the molecular profiling of AML patients before treatment is commonplace and crucial for ensuring that patients receive the most optimal therapy for any driver mutations they may have. Here, we detail the current targeted therapies available for AML: specifically, those targeting the BCL2 family (venetoclax), FLT3 (midostaurin, gilteritinib, quizartinib), IDH1/2 (enasidenib, ivosidenib), and MENIN (revumenib, ziftomenib). In addition, we outline potential mechanisms of resistance against these therapies, as well as efforts being taken to prevent or bypass them.

BCL2↗
PubMed2025

Relationship Between Cognitive Disorder and First-Line Targeted Therapy for Oncogene Driver-Positive Patients With Non-Small Cell Lung Cancer: Prospective Cohort Study.

BACKGROUND: Previous studies have found and confirmed a correlation between cognitive disorder and chemotherapy. As genetic testing becomes more routine in clinical practice, targeted therapies are increasingly gaining prominence. The relationship between targeted treatment and cognitive function is not yet clear. This study aimed to investigate the correlation between cognitive disorder and targeted treatment by evaluating the changes in cognitive function before and after targeted therapy. OBJECTIVE: This study aims to explore whether targeted therapy affects cognitive function in patients with advanced lung cancer and to explore the association between cognitive function, the inflammatory biomarker C-reactive protein, and psychological stress. METHODS: From the screened cohort of 150 patients with advanced non-small cell lung cancer (NSCLC) with gene mutations, 87 (58%) were rigorously selected for the study. The evaluation instruments used were the Mini-Mental State Examination scale, the Distress Thermometer, and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 for assessing quality of life. RESULTS: A significantly lower progression-free survival (PFS) was observed in the group of patients surviving advanced NSCLC with cognitive disorder under targeted therapy in contrast to survivors in the group with no cognitive disorder (hazard ratio=0.347, 95% CI 0.209-0.578; P<.001). Furthermore, the objective response rate and disease control rate for the group with cognitive disorder were noted to be 37.8% and 86.7%, respectively, contrastingly lower than those in the group with no cognitive disorder, recorded at 78.6% and 97.6%, respectively. Significant variances were also noted in the Mini-Mental State Examination scores between patients with and without cognitive disorder both before and after targeted therapy (P<.001 in both cases), with a decreasing trend observed in both groups after targeted therapy. Noteworthy differences were found in quality of life scores both before and after targeted therapy (P<.001 in both cases). In addition, notable disparities were apparent in C-reactive protein levels among the 2 groups before and after treatment (P=.03 and P=.048 for each time point, respectively), with an upward trend observed in both groups after targeted therapy. The multivariate Cox regression analysis demonstrated that cognitive function is an independent risk factor for PFS in patients with NSCLC receiving targeted therapy. CONCLUSIONS: Cognitive disorder may lead to lower quality of life scores and shorter PFS in patients undergoing targeted therapy. Early screening and intervention for such patients could effectively improve clinical outcomes and quality of life.

Humans↗
PubMed2007

[Role of epigenetics in the carcinogenesis of head and neck carcinomas - possible new targeted therapy?].

In search of new targeted therapies for squamous cell carcinoma of the head neck (HNSCC), a better understanding of the carcinogenesis is of outmost importance. Recent studies show that not only genetic but also epigenetic alterations initiate the multistep process of tumordevelopment. Epigenetic changes lead to altered gene expression without alterations of the DNA sequence. The best characterized epigenetic change is the methylation of the promoter region of genes, especially of tumorsuppressor genes. The methylation of the promoter region blocks the promoter and therefore represses transcription. The loss of the gene products of tumorsuppressor genes leads to increased proliferation and decreased apoptosis. Methylation of tumorsuppressor genes was shown in precancerous lesions of HNSCC, which emphasizes the importance of methylation as an early biomarker. Several studies of tumor cell cultures show reactivated expression of proteins and as a result reduction of proliferation and induction of apoptosis after treatment with demethylating agentens. This presents a very promising new option for a targeted therapy.

Antimetabolites, Antineoplastic↗
PubMedDate not supplied

The challenging estrogen receptor-negative/ progesterone receptor-negative/HER-2-negative patient: a promising candidate for epidermal growth factor receptor-targeted therapy?

While epidermal growth factor receptor (EGFR)-targeted therapy has been very promising in a number of human malignancies, to date these targeted biologic agents have not proven effective in breast cancer. However, the EGFR tyrosinase inhibitors have been used indiscriminately against all types of breast tumors, perhaps missing a subpopulation of patients who may be prime candidates for EGFR-targeted therapy. In this communication we propose that patients with estrogen receptor (ER)-negative/progesterone receptor (PR)-negative/HER-2-negative tumors, which currently present a therapeutic challenge for the oncologist, may be the subgroup of breast cancer patients that might benefit from specific EGFR-targeted therapies.

Adult↗
PubMed2004

Targeted therapies in myeloid leukemia.

Targeted therapies for hematological malignancies have come of age since the advent of all trans retinoic acid (ATRA) for treating APL and STI571/Imatinib Mesylate/Gleevec for CML. There are good molecular targets for other malignancies and several new drugs are in clinical trials. In this review, we will concentrate on individual abnormalities that exist in the myelodysplastic syndromes (MDS) and myeloid leukemias that are targets for small molecule therapies (summarised in Fig. 1). We will cover fusion proteins that are produced as a result of translocations, including BCR-ABL, the FLT3 tyrosine kinase receptor and RAS. Progression of diseases such as MDS to secondary AML occur as a result of changes in the balance between cell proliferation and apoptosis and we will review targets in both these areas, including reversal of epigenetic silencing of genes such as p15(INK4B).

Animals↗
PubMed2003

Gene therapy targeting in the central nervous system.

Targeted gene therapy aims at achieving the expression of therapeutic transgenes in specific and restricted cell populations, thus sparing all other cells of the unwanted effects of the gene product. This strategy is particularly appealing for therapy of the central nervous system (CNS), where many different cell types exist, and where the inappropriate expression of a molecule can produce grave consequences. To accomplish the objectives of targeted gene therapy, two different approaches have been developed. The first one consists in creating vectors that will deliver the transgene exclusively to the selected cells, that is manipulating the transductional capacities of the vector, and the second one is based on the transcriptional properties of the transgene, so that it will only be expressed in cells where the appropriate transcriptional machinery is present. Reaching the goals of targeted gene expression will greatly increase the specificity and safety of gene therapy, thus getting us closer to the fulfillment of the expectations generated by this new branch of molecular medicine.

Adenoviridae↗
PubMed2003

Targeted therapy in non-small cell lung cancer: myth or reality.

In oncology, the term 'targeted therapy' is used to describe drugs that target only the cancer cells and spare normal cells thereby reducing host toxicity while simultaneously increasing the eradication of cancer. Trastuzumab and imatinib are well known examples of successful targeted therapy. Newer agents like gefitinib and cetuximab offer hope that targeted therapy also may yield therapeutic benefit for such refractory malignancies as lung and colon cancers. One of many remaining challenges is to identify markers, molecular or clinical, that predict for responsiveness to a specific targeted therapy (e.g. HER2/neu positivity and trastuzumab responsiveness). However, using emerging technologies such as gene or protein profiling, it may be possible to predict a tumor's responsiveness to a particular targeted therapy based on its molecular signature. If true, clinicians might then possess the ability to predict a tumor's clinical behavior and shape its density through specific, targeted interventions.

Antineoplastic Agents↗
PubMed2005

Targeted therapy for epithelial ovarian cancer.

Ovarian cancer is the leading cause of death in women with gynecological malignancies and overall survival for patients with advanced epithelial ovarian cancer (EOC) remains poor. The majority of patients recur after initial treatment. A strategy for improving outcome is to minimise recurrence via targeted therapy in patients after front-line therapy, or more appropriately as consolidation therapy. EOC represents an attractive target because of the biology of the disease and that the bulk of disease occurs in the peritoneal cavity. To initiate targeted therapy, a candidate target must be identified. Innovative approaches via targeted therapy to control metastatic residual EOC are currently under investigation. The targets are molecules and pathways, on which cancer cells depend to proliferate, invade, metastasise and prevent apoptosis. Potential targeted therapies include: proapoptototic therapy, suicide gene therapy, signal transduction, antiangiogenesis, immunotherapy and cytokine therapy. The utilisation of these targets in the clinic demands carefully conducted, well-coordinated but discovery-oriented translational research in the form of clinical trials that can quickly assess alternative strategies or combination of strategies that could result in clinical benefit. Therefore, targeted therapy for epithelial ovarian cancer, especially after complete response to standard regimens, represents a paradigm whose time has come to be nurtured.

Antineoplastic Agents↗