• Tuberculosis and Respiratory Diseases
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• 제86권1호
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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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• 제14권5호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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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.

• Biomolecules & Therapeutics
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• 제19권4호
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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.

• Journal of Industrial and Engineering Chemistry
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• 제67권
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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.

• Journal of Digestive Cancer Research
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• 제3권1호
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• pp.5-10
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• 2015

With advances in the understanding of the biology and genetics of colorectal cancer (CRC), diagnostic biomarkers that may predict the existence or future presence of cancer or a hereditary condition, and prognostic and treatment biomarkers that may direct the approach to therapy have been developed. Biomarkers can be ascertained and assayed from any tissue that may demonstrate the diagnostic or prognostic value, including from blood cells, epithelial cells via buccal swab, fresh or archival cancer tissue, as well as from cells shed into fecal material. For CRC, current examples of biomarkers for screening and surveillance include germline testing for suspected hereditary CRC syndromes, and stool DNA tests for screening average at-risk patients. Molecular biomarkers for CRC that may alter patient care and treatment include the presence or absence of microsatellite instability, the presence or absence of mutant KRAS, BRAF or PIK3CA, and the level of expression of 15-PGDH in the colorectal mucosa. Molecularly targeted therapies and some general therapeutic approaches rely on biomarker information. Additional novel biomarkers are on the horizon that will undoubtedly further the approach to precision or individualized medicine.

• Radiation Oncology Journal
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• 제37권4호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제16권10호
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• pp.4147-4156
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• 2015

Lung cancer is a serious health problem and leading cause of death worldwide due to its high incidence and mortality. More than 80% of lung cancers feature a non-small cell histology. Over few decades, systemic chemotherapy and surgery are the only treatment options in this type of tumor but due to their limited efficacy and overall poor survival of patients, there is an urge to develop newer therapeutic strategies which circumvent the problems. Enhanced knowledge of translational science and molecular biology have revealed that lung tumors carry diverse driver gene mutations and adopt different intracellular pathways leading to carcinogenesis. Hence, the development of targeted agents against molecular subgroups harboring critical mutations is an attractive approach for therapeutic treatment. Targeted therapies are clearly more preferred nowadays over systemic therapies because they target tumor specific molecules resulting with enhanced activity and reduced toxicity to normal tissues. Thus, this review encompasses comprehensive updates on targeted therapies for the driver mutations in non-small cell lung cancer (NSCLC) and the potential challenges of acquired drug resistance faced i n the field of targeted therapy along with the imminent newer treatment modalities against lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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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.

• Tuberculosis and Respiratory Diseases
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• 제87권1호
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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.