• 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.

• 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.

• Tuberculosis and Respiratory Diseases
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• v.86 no.1
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• pp.1-13
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• 2023

Lung cancer ranks first in cancer mortality in Korea and cancer incidence in Korean men. More than half of Korean lung cancer patients undergo chemotherapy, including adjuvant therapy. Cytotoxic agents, targeted therapy, and immune checkpoint inhibitors are used in chemotherapy according to the biopsy and genetic test results. Among chemotherapy, the one that has developed rapidly is targeted therapy. The National Comprehensive Cancer Network (NCCN) guidelines have been updated recently for targeted therapy of multiple gene mutations, and targeted therapy is used not only for chemotherapy but also for adjuvant therapy. While previously targeted therapies have been developed for common genetic mutations, recently targeted therapies have been developed to overcome uncommon mutations or drug resistance that have occurred since previous targeted therapy. Therefore, this study describes recent, rapidly developing targeted therapies.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7421-7426
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• 2013

Background: Colorectal cancer is the fourth most common cancer worldwide and the second leading cause of cancer-related death. FOLFOX is the most common regimen used in the first-line chemotherapy in advanced colorectal cancer, but only half of the patients respond to this regimen and we have almost no clue in predicting resistance in such first-line application. Methods: To explore the potential molecular biomarkers predicting the resistance of FOLFOX regimen as the first-line treatment in advanced colorectal cancer, we screened microRNAs in serum samples from drug-responsive and drug-resistant patients by microarrays. Then differential microRNA expression was further validated in an independent population by reverse transcription and quantitative real-time PCR. Results: 62 microRNAs expressing differentially with fold-change >2 were screened out by microarray analysis. Among them, 5 (miR-221, miR-222, miR-122, miR-19a, miR-144) were chosen for further validation in an independent population (N=72). Our results indicated serum miR-19a to be significantly up-regulated in resistance-phase serum (p=0.009). The ROC curve analysis showed that the sensitivity of serum miR-19a to discriminate the resistant patients from the response ones was 66.7%, and the specificity was 63.9% when the AUC was 0.679. We additionally observed serum miR-19a had a complementary value for cancer embryonic antigen (CEA). Stratified analysis further revealed that serum miR-19a predicted both intrinsic and acquired drug resistance. Conclusions: Our findings confirmed aberrant expression of serum miR-19a in FOLFOX chemotherapy resistance patients, suggesting serum miR-19a could be a potential molecular biomarker for predicting and monitoring resistance to first-line FOLFOX chemotherapy regimens in advanced colorectal cancer patients.

• 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.

• 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.

• Nuclear Medicine and Molecular Imaging
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• v.40 no.2
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• pp.74-81
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• 2006

Molecular targeting may be defined as the specific concentration of a diagnostic or therapeutic tracer by its Interaction with a molecular species that is distinctly present or absent in a disease state. Monoclonal antibody (mAb) is one of the successful agents for targeted therapy in cancer. To enhance the therapeutic effect, the concept of targeting radionuclides to tumors using radiolabeled mAbs against tumor-associated antigens, radioimmunotherapy, was proposed. The efficacy of radioimmunotherapy, however, has to be further optimized. Several strategies to improve targeting of tumors with radiolabeled mAbs have been developed, such as the use of mAb fragments, the use of high-affinity mAbs, the use of labeling techniques that are stable in vivo, active removal of the radiolabeled mAb from the circulation, and pretargeting strategies. Until now, however, there are many kinds of obstacles to be solved in the use of mAb for the targeted therapy. Major technical challenges to molecular targeting are related to the rapid and specific delivery of tracers to the target, the elimination of unwanted background activity, and the development of more specific targets to create a cytocidal effect. further development of this field will be determined by success in solving these challenges.

• 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.

• 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.

• Tuberculosis and Respiratory Diseases
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• v.87 no.1
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• pp.31-39
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• 2024

After the successful development of targeted therapy and immunotherapy for the treatment of advanced-stage non-small cell lung cancer (NSCLC), these innovative treatment options are rapidly being applied in the adjuvant setting for early-stage NSCLC. Some adjuvants that have recently been approved include osimertinib for epidermal growth factor receptor-mutated tumors and atezolizumab and pembrolizumab for selected patients with resectable NSCLC. Numerous studies on various targeted therapies and immunotherapy with or without chemotherapy are currently ongoing in the adjuvant setting. However, several questions regarding optimal strategies for adjuvant treatment remain unanswered. The present review summarizes the available literature, focusing on recent advances and ongoing trials with targeted therapy and immunotherapy in the adjuvant treatment of early-stage NSCLC.