• Title, Summary, Keyword: targeted therapy

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Application of Stem Cells in Targeted Therapy of Breast Cancer: A Systematic Review

  • Madjd, Zahra;Gheytanchi, Elmira;Erfani, Elham;Asadi-Lari, Mohsen
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.5
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    • pp.2789-2800
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    • 2013
  • Background: The aim of this systematic review was to investigate whether stem cells could be effectively applied in targeted therapy of breast cancer. Material and Method: A systematic literature search was performed for original articles published from January 2007 until May 2012. Results: Nine studies met the inclusion criteria for phase I or II clinical trials, of which three used stem cells as vehicles, two trials used autologous hematopoetic stem cells and in four trials cancer stem cells were targeted. Mesenchymal stem cells (MSCs) were applied as cellular vehicles to transfer therapeutic agents. Cell therapy with MSC can successfully target resistant cancers. Cancer stem cells were selectively targeted via a proteasome-dependent suicide gene leading to tumor regression. $Wnt/{\beta}$-catenin signaling pathway has been also evidenced to be an attractive CSC-target. Conclusions: This systematic review focused on two different concepts of stem cells and breast cancer marking a turning point in the trials that applied stem cells as cellular vehicles for targeted delivery therapy as well as CSC-targeted therapies. Applying stem cells as targeted therapy could be an effective therapeutic approach for treatment of breast cancer in the clinic and in therapeutic marketing; however this needs to be confirmed with further clinical investigations.

Extracranial systemic antitumor response through the abscopal effect induced by brain radiation in a patient with metastatic melanoma

  • D'Andrea, Mark A.;Reddy, G.K.
    • Radiation Oncology Journal
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    • v.37 no.4
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    • pp.302-308
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    • 2019
  • The abscopal effect is a term that has been used to describe the phenomenon in which localized radiation therapy treatment of a tumor lesion triggers a spontaneous regression of metastatic lesion(s) at a non-irradiated distant site(s). Radiation therapy induced abscopal effects are believed to be mediated by activation and stimulation of the immune system. However, due to the brain's distinctive immune microenvironment, extracranial abscopal responses following cranial radiation therapy have rarely been reported. In this report, we describe the case of 42-year-old female patient with metastatic melanoma who experienced an abscopal response following her cranial radiation therapy for her brain metastasis. The patient initially presented with a stage III melanoma of the right upper skin of her back. Approximately 5 years after her diagnosis, the patient developed a large metastatic lesion in her upper right pectoral region of her chest wall and axilla. Since the patient's tumor was positive for BRAF and MEK, targeted therapy with dabrafenib and trametinib was initiated. However, the patient experienced central nervous system (CNS) symptoms of headache and disequilibrium and developed brain metastases prior to the start of targeted therapy. The patient received radiation therapy to a dose of 30 Gy delivered in 15 fractions to her brain lesions while the patient was on dabrafenib and trametinib therapy. The patient's CNS metastases improved significantly within weeks of her therapy. The patient's non-irradiated large extracranial chest mass and axilla mass also shrank substantially demonstrating the abscopal effect during her CNS radiation therapy. Following radiation therapy of her residual chest lesions, the patient was disease free clinically and her CNS lesions had regressed. However, when the radiation therapy ended and the patient continued her targeted therapy alone, recurrence outside of her previously treated fields was noted. The disease recurrence could be due to the possibility of developing BRAF resistance clones to the BRAF targeted therapy. The patient died eventually due to wide spread systemic disease recurrence despite targeted therapy.

Molecular Targeting Agents in Cancer Therapy: Science and Society

  • Shaikh, Asim Jamal
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.4
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    • pp.1705-1708
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    • 2012
  • The inception of targeted agents has revolutionized the cancer therapy paradigm, both for physicians and patients. A large number of molecular targeted agents for cancer therapy are currently available for clinical use today. Many more are in making, but there are issues that remain to be resolved for the scientific as well as social community before the recommendation of their widespread use in may clinical scenarios can be done, one such issue being cost and cost effectiveness, others being resistance and lack of sustained efficacy. With the current knowledge about available targeted agents, the growing knowledge of intricate molecular pathways and unfolding of wider spectrum of molecular targets that can really matter in the disease control, calls for only the just use of the agents available now, drug companies need to make a serious attempt to reduce the cost of the agents. Research should focus on agents that show sustained responses in preclinical data. More needs to be done in laboratories and by the pharmaceutical industries, before we can truly claim to have entered a new era of targeted therapy in cancer care.

Treatment outcome of radiation therapy and concurrent targeted molecular therapy in spinal metastasis from renal cell carcinoma

  • Park, Sangjoon;Kim, Kyung Hwan;Rhee, Woo Joong;Lee, Jeongshim;Cho, Yeona;Koom, Woong Sub
    • Radiation Oncology Journal
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    • v.34 no.2
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    • pp.128-134
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    • 2016
  • Purpose: To evaluate the clinical outcomes of patients who underwent radiation therapy with or without targeted molecular therapy for the treatment of spinal metastasis from renal cell carcinoma (RCC). Materials and Methods: A total of 28 spinal metastatic lesions from RCC patients treated with radiotherapy between June 2009 and June 2015 were retrospectively reviewed. Thirteen lesions were treated concurrently with targeted molecular therapy (concurrent group) and 15 lesions were not (nonconcurrent group). Local control was defined as lack of radiographically evident local progression and neurological deterioration. Results: At a median follow-up of 11 months (range, 2 to 58 months), the 1-year local progression-free rate (LPFR) was 67.0%. The patients with concurrent targeted molecular therapy showed significantly higher LPFR than those without (p = 0.019). After multivariate analysis, use of concurrent targeted molecular therapy showed a tendency towards improved LPFR (hazard ratio, 0.13; 95% confidence interval, 0.01 to 1.16). There was no difference in the incidence of systemic progression between concurrent and nonconcurrent groups. No grade ${\geq}2$ toxicities were observed during or after radiotherapy. Conclusion: Our study suggests the possibility that concurrent use of targeted molecular therapy during radiotherapy may improve LPFR. Further study with a large population is required to confirm these results.

Future Cancer Therapy with Molecularly Targeted Therapeutics: Challenges and Strategies

  • Kim, Mi-Sook
    • Biomolecules & Therapeutics
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    • v.19 no.4
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    • pp.371-389
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    • 2011
  • A new strategy for cancer therapy has emerged during the past decade based on molecular targets that are less likely to be essential in all cells in the body, therefore confer a wider therapeutic window than traditional cytotoxic drugs which mechanism of action is to inhibit essential cellular functions. Exceptional heterogeneity and adaptability of cancer impose significant challenges in oncology drug discovery, and the concept of complex tumor biology has led the framework of developing many anticancer therapeutics. Protein kinases are the most pursued targets in oncology drug discovery. To date, 12 small molecule kinase inhibitors have been approved by US Food and Drug Administration, and many more are in clinical development. With demonstrated clinical efficacy of bortezomib, ubiquitin proteasome and ubiquitin-like protein conjugation systems are also emerging as new therapeutic targets in cancer therapy. In this review, strategies of targeted cancer therapies with inhibitors of kinases and proteasome systems are discussed. Combinational cancer therapy to overcome drug resistance and to achieve greater treatment benefit through the additive or synergistic effects of each individual agent is also discussed. Finally, the opportunities in the future cancer therapy with molecularly targeted anticancer therapeutics are addressed.

Cancer-targeted photothermal therapy using aptamer-conjugated gold nanoparticles

  • Hong, Eun Ji;Kim, Yoon-Seok;Choi, Dae Gun;Shim, Min Suk
    • Journal of Industrial and Engineering Chemistry
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    • v.67
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    • pp.429-436
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    • 2018
  • Targeted intracellular delivery of therapeutic agents is one of the great challenges for cancer treatment. Aptamers that bind to a variety of biological targets have emerged as new targeting moieties with high specificity for targeted cancer therapy. In this study, near-infrared (NIR) light-absorbing hollow gold nanocages (AuNCs) were synthesized and conjugated with AS1411 aptamer to achieve cancer-targeted photothermal therapy. AuNC functionalized with PEG and AS1411 (AS1411-PEG-AuNC) exhibited selective cellular uptake in breast cancer cells due to selective binding of AS1411 to nucleolin, a protein that is over-expressed in cancer cells over normal cells. As a result, AS1411-PEG-AuNC showed cancer-targeted photothermal activity. This study demonstrates that aptamer-conjugated AuNCs are effective tumor-targeting photothermal agents.

Targeted Polymeric Gene Delivery for Anti-angiogenic Tumor Therapy

  • Kim, Won-Jong;Kim, Sung-Wan
    • Macromolecular research
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    • v.15 no.2
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    • pp.100-108
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    • 2007
  • Gene therapy has become a promising strategy for the treatment of genetically based diseases, such as cancer, which are currently considered incurable. A major obstacle in the field of cancer gene therapy is the development of a safe and efficient delivery system for therapeutic gene transfer. Non-viral vectors have attracted great interest, as they are simple to prepare, stable, easy to modify and relatively safe compared to viral vectors. In this review, an insight into the strategies developed for polyethylenimine (PEI)-based non-viral vectors has been provide, including improvement of the polyplex properties by incorporating hydrophilic spacer, poly(ethylene glycol) (PEG). Moreover, this review will summarize the strategies for the tumor targeting. Specifically, a targeted polymeric gene delivery system, PEI-g-PEG-RGD, will be introduced as an efficient gene delivery vector for tumor therapy, including its functional analysis both in vitro and in vivo.

Comparative Analysis of the Seriousness of the Adverse Events and Risk of Targeted Therapy for Metastatic Renal Cell Carcinoma Among Medical Professionals (전이성신세포암 표적치료제의 부작용 심각도 및 위해에 대한 전문가그룹별 비교분석)

  • Park, Mi-Hae;Rhee, Jin-Nie;Lee, Eui-Kyung
    • Korean Journal of Clinical Pharmacy
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    • v.21 no.2
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    • pp.100-105
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    • 2011
  • The perception of the 20 adverse events of targeted therapy for metastatic renal cell carcinoma was compared among medical professionals. Thirty-seven oncologists, 167 nurses and 79 pharmacists participated in the survey, and the response rate was 61.9%, 98.2%, 84.9%, respectively. Results showed that the most serious adverse event was GI perforation (8.83 points, 10 being the most serious), whereas the least serious was anemia (5.32 points). There were significant differences among oncologists, nurses and pharmacists especially for the moderately-serious adverse event such as wound-healing complication and lymphopenia. Adverse Events Composite Score (AECS) for each targeted therapy was calculated by multiplying adverse event incidence rate and seriousness score. Sunitinib had the highest score at 6.86 point and bevacizumab had the lowest at 2.1. Among professional groups oncologists showed the lowest AECS, whereas nurses had the highest. The gap on the perception of the adverse events among medical professionals needs to be reduced to get better outcomes of medical therapies for cancer patients.

211At and 211At-labeled radiopharmaceuticals for targeted alpha therapy

  • Kang, Choong Mo;Lee, Kyo Chul;Lee, Yong Jin
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.4 no.2
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    • pp.99-105
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    • 2018
  • $^{211}At$ is an alpha emitting radionuclide, which can be produced using cyclotron with alpha beam. In addition, its strong linear energy transfer and iodine-like chemistry make that $^{211}At$ is one of the most attractive radionuclide in the field of targeted alpha therapy. In this review, production, labeling, and radiopharmaceuticals of $^{211}At$ will be discussed.

Targeted alpha therapy (TAT) for cancer using metallic radioisotopes

  • Kang, Chi Soo;Lee, Kyo Chul;Lee, Yong Jin
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.5 no.2
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    • pp.135-144
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    • 2019
  • Targeted alpha therapy (TAT) based on metallic radionuclides has attracted a lot of attention lately due to its impressive therapeutic efficacy displayed in couple of clinical studies for cancer. Representative metallic radionuclides emitting alpha-particle include 225Ac, 213Bi, and 227Th, and there have been variety of TAT formulations based on different targeting moiety and chelating agents. In this review, we introduce strategies to label metallic radioisotopes with biomolecules and look at some of recent preclinical and clinical results of TAT for cancer.