• Title/Summary/Keyword: Therapy-refractory cancer

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Anticancer Therapy for Breast Cancer Patients with Skin Metastases Refractory to Conventional Treatments

  • Varol, Umut;Yildiz, Ibrahim;Alacacioglu, Ahmet;Uslu, Ruchan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.4
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    • pp.1885-1887
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    • 2014
  • Skin metastases of breast cancer are usually late events in the course of tumor progression and signify a poor prognosis. They may remain as a therapeutic challenge especially after failure of standard treatments. Topical interventions, together with or without radiotherapy, may only palliate the symptoms temporarily. However, there may be alternative treatment modalities for unresectable breast cancer skin metastases resistant to chemotherapy and radiotherapy. There are various genetic alterations in tumors and therapeutic potential of expression patterns for factors like epidermal growth factor receptor may have important clinical implications in case of disease refractory to the conventional treatments. Here, we clarified the therapeutic options and genetic alterations in skin metastatic breast cancer patients refractory to standard chemotherapeutics.

Far Beyond Cancer Immunotherapy: Reversion of Multi-Malignant Phenotypes of Immunotherapeutic-Resistant Cancer by Targeting the NANOG Signaling Axis

  • Se Jin Oh;Jaeyoon Lee;Yukang Kim;Kwon-Ho Song;Eunho Cho;Minsung Kim;Heejae Jung;Tae Woo Kim
    • IMMUNE NETWORK
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    • v.20 no.1
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    • pp.7.1-7.11
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    • 2020
  • Cancer immunotherapy, in the form of vaccination, adoptive cellular transfer, or immune checkpoint inhibitors, has emerged as a promising practice within the field of oncology. However, despite the developing field's potential to revolutionize cancer treatment, the presence of immunotherapeutic-resistant tumor cells in many patients present a challenge and limitation to these immunotherapies. These cells not only indicate immunotherapeutic resistance, but also show multi-modal resistance to conventional therapies, abnormal metabolism, stemness, and metastasis. How can immunotherapeutic-resistant tumor cells render multi-malignant phenotypes? We reasoned that the immune-refractory phenotype could be associated with multi-malignant phenotypes and that these phenotypes are linked together by a factor that acts as the master regulator. In this review, we discussed the role of the embryonic transcription factor NANOG as a crucial master regulator we named "common factor" in multi-malignant phenotypes and presented strategies to overcome multi-malignancy in immunotherapeutic-resistant cancer by restraining the NANOG-mediated multi-malignant signaling axis. Strategies that blunt the NANOG axis could improve the clinical management of therapy-refractory cancer.

RhoBTB3 Regulates Proliferation and Invasion of Breast Cancer Cells via Col1a1

  • Kim, Kyungho;Kim, Youn-Jae
    • Molecules and Cells
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    • v.45 no.9
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    • pp.631-639
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    • 2022
  • Breast cancer is the leading cause of cancer-related death in women worldwide, despite medical and technological advancements. The RhoBTB family consists of three isoforms: RhoBTB1, RhoBTB2, and RhoBTB3. RhoBTB1 and RhoBTB2 have been proposed as tumor suppressors in breast cancer. However, the roles of RhoBTB3 proteins are unknown in breast cancer. Bioinformatics analysis, including Oncomine, cBioportal, was used to evaluate the potential functions and prognostic values of RhoBTB3 and Col1a1 in breast cancer. qRT-PCR analysis and immunoblotting assay were performed to investigate relevant expression. Functional experiments including proliferation assay, invasion assay, and flow cytometry assay were conducted to determine the role of RhoBTB3 and Col1a1 in breast cancer cells. RhoBTB3 mRNA levels were significantly up-regulated in breast cancer tissues as compared to in adjacent normal tissues. Moreover, RhoBTB3 expression was found to be associated with Col1a1 expression. Decreasing RhoBTB3 expression may lead to decreases in the proliferative and invasive properties of breast cancer cells. Further, Col1a1 knockdown in breast cancer cells limited the proliferative and invasive ability of cancer cells. Knockdown of RhoBTB3 may exert inhibit the proliferation, migration, and metastasis of breast cancer cells by repressing the expression of Col1a1, providing a novel therapeutic strategy for treating breast cancer.

Recent Improvements in the Treatment of High-Risk Thyroid Cancer (예후가 좋지 않은 갑상선암에 대한 최신 치료 방침)

  • Lee, Eun Kyung
    • Korean Journal of Head & Neck Oncology
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    • v.38 no.1
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    • pp.1-9
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    • 2022
  • Thyroid cancer is one of the slow-growing tumors with excellent oncological outcomes. However, a small set of patients with unexpectedly severe outcomes are usually ignored. Anaplastic thyroid cancer (ATC) remains one of the most aggressive and lethal solid tumors. Recently, dabrafenib and trametinib combination therapy or neoadjuvant BRAF induction therapy has shown promising results. In addition, a combination of targeted drugs, immunotherapy, surgery, and radiation therapy can improve overall survival in ATC patients. Another disease for which there is no breakthrough treatment is radioactive iodine-refractory differentiated thyroid cancer (DTC). To date, multikinase inhibitors (sorafenib, lenvatinib) targeting the growth factor signaling pathway have been developed and approved as anticancer agents for patients with advanced DTC. This review includes results from multikinase inhibitors to the emergence of new target molecules, including rearrangements during transformation (RET) and tropomyosin receptor kinase (TRK).

Resveratrol Prevents Hormone-refractory Prostate Cancer Cell Growth via Inhibition of STAT3 Activity (STAT3 활성 억제를 유도하는 resveratrol의 호르몬 불응성 전립선 암 예방 효과)

  • Cho, Seok-Cheol;Choi, Bu Young
    • Korean Journal of Food Science and Technology
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    • v.46 no.4
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    • pp.516-521
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    • 2014
  • The mechanisms underlying the refractory effects of flutamide, a first-line oral anti-androgen drug, have not been entirely elucidated. In the present study, we investigated the mechanism of flutamide-induced hormone-refractory prostate cancer cell growth and its modulation by resveratrol, a phytoalexin present in grapes. Resveratrol significantly attenuated interleukin 6 (IL-6)-induced signal transducer and activator of transcription 3 (STAT3) transcriptional activity and dihydrotestosterone (DHT) or IL-6-induced prostate-specific antigen (PSA) transcriptional activity. Furthermore, compared to treatment with DHT or IL-6 alone, combination treatment of cells significantly increased PSA transcriptional activity, and resveratrol markedly diminished DHT plus IL-6-induced STAT3 and PSA transcriptional activities. Thus, the inhibitory effects of resveratrol on IL-6-, DHT-, and flutamide-induced hormone-refractory prostate cancer cell growth are partly mediated by the suppression of STAT3 reporter gene activity, suggesting that resveratrol represents a promising therapy for prostate cancer.

Continuous-infusion Ifosfamide and Doxorubicin Combination as Second-Line Chemotherapy for Recurrent or Refractory Osteosarcoma Patients in China: a Retrospective Study

  • Huang, Yu-Jing;He, Ai-Na;Sun, Yuan-Jue;Shen, Zan;Min, Da-Liu;Yao, Yang
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.6
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    • pp.2391-2395
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    • 2015
  • Objective: The aim of this retrospective study was to evaluate the feasibility and efficacy of response to continuous-infusion ifosfamide and doxorubicin combination as second-line chemotherapy for patients with recurrent or refractory osteosarcoma. Materials and Methods: Eighteen recurrent or refractory osteosarcoma patients who were treated with continuous-infusion ifosfamide and doxorubicin combination between May 1999 and April 2011 were included in the analysis. Ifosfamide at $12g/m^2$ was administered by intravenous continuous infusion over 3 days, and doxorubicin $60mg/m^2$ was administered as an intravenous bolus injection on day 1. The combination therapy was repeated every 3 weeks. Treatment was continued until evidence of disease progression or unacceptable toxicity. Results: The patients (ages 7-53 years) received a total of 42 cycles of chemotherapy (median: 2 courses; range: 2-5 courses). The overall response rate was 0% and the disease control rate was 22.3%, with four patients having stable disease. The median time to progression and overall survival time were 2 months (range: 2-5 months) and 9 months (range: 3-29 months), respectively. Major severe toxicities were leucopenia 7 (38.9%), nausea and vomiting 3 (16.7%) and alopecia 9 (50%). There were no treatment-related deaths. Conclusions: In our experience, continuous-infusion ifosfamide and doxorubicin combination therapy at this dosage and schedule was found to be well tolerated and moderate effective, which could be considered as salvage therapy for patients with recurrent or refractory osteosarcoma. Further assessment is necessary to confirm the safety and efficacy of this treatment.

What's New in Molecular Targeted Therapies for Thyroid Cancer? (갑상선암 표적치료의 최신지견)

  • Min, Seonyoung;Kang, Hyunseok
    • Korean Journal of Head & Neck Oncology
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    • v.37 no.2
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    • pp.1-9
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    • 2021
  • Thyroid cancer refers to various cancers arising from thyroid gland. Differentiated thyroid cancers (DTCs) include papillary, follicular, and Hurthle cell carcinomas and represent cancers retain normal thyroid functions such as iodine uptake. Radioactive iodine (RAI) is generally used for upfront treatment of metastatic DTCs, but RAI refractory DTCs remain to be clinical challenges. Sorafenib and lenvatinib were approved for the treatment of RAI refractory DTCs and more recently, genomics-based targeted therapies have been developed for NTRK and RET gene fusion-positive DTCs. Poorly differentiated and anaplastic thyroid cancers (ATCs) are extremely challenging diseases with aggressive courses. BRAF/MEK inhibition has been proven to be highly effective in BRAF V600E mutation-positive ATCs and immune checkpoint inhibitors have shown promising activities. Medullary thyroid cancers, which arise from parafollicular cells of thyroid, represent a unique subset of thyroid cancer and mainly driven by RET mutation. In addition to vandetanib and cabozantinib, highly specific RET inhibitors such as selpercatinib and pralsetinib have demonstrated impressive activity and are in clinical use.

The Concurrent Use of Rhus verniciflua Stokes as Complementary Therapy with Second or More Line Regimens on Advanced Non-small-cell Lung Cancer: Case Series

  • Lee, Sang-Hun;Kim, Kyung-Suk;Choi, Won-Cheol;Yoon, Seong-Woo
    • The Journal of Korean Medicine
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    • v.30 no.6
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    • pp.112-117
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    • 2009
  • Objective: Rhus verniciflua Stokes (RVS) has anticancer effect confirmed by preclinical studies and historical records. We thus tried to evaluate retrospectively the effect of RVS as a complementary medicine for patients with advanced non-small-cell lung cancer (NSCLC) showing refractory to conventional chemotherapy. Patients and Methods: From June 1, 2006 to June 30, 2007, patients with advanced NSCLC who received both the standardized RVS extract and a standard course of second or more line therapy such as pemetrexed ($Alimta^{(R)}$), erlotinib ($Tarceva^{(R)}$), and gefitinib ($Iressa^{(R)}$) were checked. A total of 13 patients were eligible for the final analysis after fulfilling inclusion/exclusion criteria. Time to progression (TTP) of these patients treated with the standardized RVS extract was checked in the aftercare period. Results: Patients received RVS treatment for a median period of 296 (range 84-698) days. The median TTP was 220.5 (range 36-489) days, and three patients (23.1%) had TTP values of 15 more months. No significant side effects from RVS treatment have been observed. Conclusion: The standardized RVS extract might have synergetic effects by assisting apoptosis in advanced NSCLC with concurrent standard therapy agents, since it prolonged TTP without significant adverse effects. This study suggests that the standardized RVS extract is beneficial to patients with chemotherapy-refractory NSCLC. Further clinical trials and preclinical studies are necessary to determine the efficacy and safety of the standardized RVS extract in NSCLC.

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Retinoic Acid Redifferentiation Therapy for Papillary Carcinoma of Thyroid with Negative Radioiodine Uptake (방사성옥소 섭취를 보이지 않은 갑상선 유두암에서 Retinoic acid 치료)

  • Bae, Sang-Kyun;Yum, Ha-Yong
    • The Korean Journal of Nuclear Medicine
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    • v.35 no.6
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    • pp.393-397
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    • 2001
  • Surgery, radioiodine therapy, and thyroxine treatment represent established therapeutic measures of proven efficacy for the treatment of well-differentiated thyroid cancer. However, in some cases, dedifferentiation is noted and it makes tumors refractory to conventional treatment. Recently, retinoic acid redifferentiation therapy was evaluated in several in vitro and in vivo studios. We report a patient with papillary carcinoma in whom metastatic lesions became radioiodine negative on high-dose therapy. Redifferentiation therapy with retinoic acid induced radioiodine uptake in some of metastatic tissues. Side effects such as xerostomia and cheilosis were mild. We recommend retinoic acid redifferentiation therapy as an option for the treatment of thyroid cancer with negative radioiodine uptake after high-dose radioiodine therapy.

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