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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (18 August 2023) | Viewed by 11796

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Special Issue Editor

Prof. Dr. Kazuko Kaneda-Nakashima

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Institute for Radiation Sciences, Osaka University, 2-4 Suita, Osaka 565-0871, Japan
Interests: biochemistry; radiobiology; pharmacology; molecular science; radiochemistry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

In recent years, the survival rate of cancer patients has increased, due to the development of various treatments. However, some cancers, such as pancreatic cancer, are extremely resistant to treatment. One approach uses antibodies or chemicals conjugated to radionuclides, which provide specific radiotherapy. Several cancer-specific molecular targets (such as LAT1, highly expressed in tumor tissues) have been selected, and antibodies (i.e., ⁹⁰Y-CD20 and ¹¹¹In-CD20 antibodies, Zevalin®) have also been selected. Nuclear medicine treatment is less invasive than surgery, and is suitable for difficult-to-treat cancer cases. In particular, targeted α therapy (TAT) involves the selective delivery of α-emitters to tumors, using high linear energy transfer (LET) α-particles, while minimizing the damage caused to surrounding tissues. Radium-223 (²²³Ra) dichloride has been employed as a treatment for bone metastasis (i.e., Xofigo®), as well as for pain management. Radiopharmaceuticals constitute a practical and effective treatment, albeit with their restrictions. Actinium-225 (²²⁵At) and astatine-211 (²¹¹At) are promising radionuclides for TAT.

We focus on researching the usefulness of nuclear medicine treatments, and we aim to drive the development of novel therapeutic agents. Since molecular biology and basic scientific studies are indispensable for the development of technology in nuclear medicine, we will prioritize basic research over clinical trials/data.

Prof. Dr. Kazuko Kaneda-Nakashima
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

TAT (targeting alpha therapy)
nuclear medicine
cancer treatment
imaging
radioisotope (RI)
surface marker
TRT (targeted radioisotope therapy)

Published Papers (5 papers)

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Research

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15 pages, 8114 KiB

Open AccessArticle

Increased Chymase-Positive Mast Cells in High-Grade Mucoepidermoid Carcinoma of the Parotid Gland

by Hiromi Nishimura, Denan Jin, Ichita Kinoshita, Masataka Taniuchi, Masaaki Higashino, Tetsuya Terada, Shinji Takai and Ryo Kawata

Int. J. Mol. Sci. 2023, 24(9), 8267; https://doi.org/10.3390/ijms24098267 - 5 May 2023

Cited by 1 | Viewed by 1472

Abstract

It has long been known that high-grade mucoepidermoid carcinoma (MEC) has a poor prognosis, but the detailed molecular and biological mechanisms underlying this are not fully understood. In the present study, the pattern of chymase-positive mast cells, as well as chymase gene expression, in high-grade MEC was compared to that of low-grade and intermediate-grade MEC by using 44 resected tumor samples of MEC of the parotid gland. Chymase expression, as well as chymase-positive mast cells, was found to be markedly increased in high-grade MEC. Significant increases in PCNA-positive cells and VEGF gene expression, as well as lymphangiogenesis, were also confirmed in high-grade MEC. Chymase substrates, such as the latent transforming growth factor-beta (TGF-β) 1 and pro-matrix metalloproteinase (MMP)-9, were also detected immunohistologically in high-grade MEC. These findings suggested that the increased chymase activity may increase proliferative activity, as well as metastasis in the malignant condition, and the inhibition of chymase may be a strategy to improve the poor prognosis of high-grade MEC of the parotid gland. Full article

(This article belongs to the Special Issue Targeted Treatments in Cancer)

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8 pages, 2294 KiB

Open AccessArticle

Effect to Therapy of Sodium-Iodine Symporter Expression by Alpha-Ray Therapeutic Agent via Sodium/Iodine Symporter

by Kazuko Kaneda-Nakashima, Yoshifumi Shirakami, Tadashi Watabe, Kazuhiro Ooe, Takashi Yoshimura, Atsushi Toyoshima, Yang Wang, Hiromitsu Haba and Koichi Fukase

Int. J. Mol. Sci. 2022, 23(24), 15509; https://doi.org/10.3390/ijms232415509 - 7 Dec 2022

Cited by 2 | Viewed by 1356

Abstract

This study confirmed the effect of sodium/iodine symporter (NIS) expression on existing drugs by in vitro and in vivo tests using cultured cell lines. The tumor growth inhibitory effect of sodium astatide ([²¹¹At]NaAt) was evaluated by in vitro and in vivo tests using human thyroid cancer cells (K1, K1/NIS and K1/NIS-DOX). NIS expression in cancer cells was controlled using the Tet-On system. [¹³¹I]NaI was used as control existing drug. From the results of the in vitro studies, the mechanism of [²¹¹At]NaAt uptake into thyroid cancer cells is mediated by NIS, analogous to [¹³¹I]NaI, and the cellular uptake rate correlates with the expression level of NIS. [²¹¹At]NaAt’s ability to inhibit colony formation was more than 10 times that of [¹³¹I]NaI per becquerel (Bq), and [²¹¹At]NaAt’s DNA double-strand breaking (DSB) induction was more than ten times that of [¹³¹I]NaI per Bq, and [²¹¹At]NaAt was more than three times more cytotoxic than [¹³¹I]NaI (at 1000 kBq each). In vivo studies also showed that the tumor growth inhibitory effect of [²¹¹At]NaAt depended on NIS expression and was more than six times that of [¹³¹I]NaI per Bq. Full article

(This article belongs to the Special Issue Targeted Treatments in Cancer)

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11 pages, 1583 KiB

Open AccessArticle

Efficacy of Combination Therapy with Lenvatinib and Radioactive Iodine in Thyroid Cancer Preclinical Model

by Kensuke Suzuki, Hiroshi Iwai, Keita Utsunomiya, Yumiko Kono, Tadashi Watabe, Yoshiki Kobayashi, Dan Van Bui, Shunsuke Sawada, Yasutaka Yun, Akitoshi Mitani, Kenta Fukui, Haruka Sakai, Hanh Hong Chu, Nguyen Manh Linh, Noboru Tanigawa and Akira Kanda

Int. J. Mol. Sci. 2022, 23(17), 9872; https://doi.org/10.3390/ijms23179872 - 30 Aug 2022

Cited by 2 | Viewed by 2101

Abstract

Patients with differentiated thyroid cancer (DTC) usually have good prognosis, while those with advanced disease have poor clinical outcomes. This study aimed to investigate the antitumor effects of combination therapy with lenvatinib and ¹³¹I (CTLI) using three different types of DTC cell lines with different profiling of sodium iodide symporter (NIS) status. The radioiodine accumulation study revealed a significantly increased radioiodine uptake in K1-NIS cells after lenvatinib treatment, while there was almost no uptake in K1 and FTC-133 cells. However, lenvatinib administration before radioiodine treatment decreased radioiodine uptake of K1-NIS xenograft tumor in the in vivo imaging study. CTLI synergistically inhibited colony formation and DTC cell migration, especially in K1-NIS cells. Finally, ¹³¹I treatment followed by lenvatinib administration significantly inhibited tumor growth of the NIS-expressing thyroid cancer xenograft model. These results provide important clinical implications for the combined therapy that lenvatinib should be administered after ¹³¹I treatment to maximize the treatment efficacy. Our synergistic treatment effects by CTLI suggested its effectiveness for RAI-avid thyroid cancer, which retains NIS function. This potential combination therapy suggests a powerful and tolerable new therapeutic strategy for advanced thyroid cancer. Full article

(This article belongs to the Special Issue Targeted Treatments in Cancer)

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Review

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29 pages, 3552 KiB

Open AccessReview

Unmasking the Deceptive Nature of Cancer Stem Cells: The Role of CD133 in Revealing Their Secrets

by Julia Pospieszna, Hanna Dams-Kozlowska, Wachirawit Udomsak, Marek Murias and Malgorzata Kucinska

Int. J. Mol. Sci. 2023, 24(13), 10910; https://doi.org/10.3390/ijms241310910 - 30 Jun 2023

Cited by 3 | Viewed by 2374

Abstract

Cancer remains a leading cause of death globally, and its complexity poses a significant challenge to effective treatment. Cancer stem cells and their markers have become key players in tumor growth and progression. CD133, a marker in various cancer types, is an active research area as a potential therapeutic target. This article explores the role of CD133 in cancer treatment, beginning with an overview of cancer statistics and an explanation of cancer stem cells and their markers. The rise of CD133 is discussed, including its structure, functions, and occurrence in different cancer types. Furthermore, the article covers CD133 as a therapeutic target, focusing on gene therapy, immunotherapy, and approaches to affect CD133 expression. Nanoparticles such as gold nanoparticles and nanoliposomes are also discussed in the context of CD133-targeted therapy. In conclusion, CD133 is a promising therapeutic target for cancer treatment. As research in this area progresses, it is hoped that CD133-targeted therapies will offer new and effective treatment options for cancer patients in the future. Full article

(This article belongs to the Special Issue Targeted Treatments in Cancer)

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13 pages, 1582 KiB

Open AccessReview

Fibroblast Activation Protein Inhibitor (FAPI)-Based Theranostics—Where We Are at and Where We Are Heading: A Systematic Review

by Marko Magdi Abdou Sidrak, Maria Silvia De Feo, Ferdinando Corica, Joana Gorica, Miriam Conte, Luca Filippi, Orazio Schillaci, Giuseppe De Vincentis and Viviana Frantellizzi

Int. J. Mol. Sci. 2023, 24(4), 3863; https://doi.org/10.3390/ijms24043863 - 15 Feb 2023

Cited by 7 | Viewed by 3679

Abstract

Cancer is the leading cause of death around the globe, followed by heart disease and stroke, with the highest mortality to this day. We have reached great levels of understanding of how these various types of cancer operate at a cellular level and this has brought us to what we call “precision medicine” where every diagnostic examination and the therapeutic procedure is tailored to the patient. FAPI is among the new tracers that can be used to assess and treat many types of cancer. The aim of this review was to gather all the known literature on FAPI theranostics. A MEDLINE search was conducted on four web libraries, PUBMED, Cochrane, Scopus, and Web of Sciences. All of the available articles that included both diagnoses and therapy with FAPI tracers were collected and put through the CASP (Critical Appraisal Skills Programme) questionnaire for systematic reviewing. A total of 8 records were deemed suitable for CASP review, ranging from 2018 to November 2022. These studies were put through the CASP diagnostic checklist, in order to assess the goal of the study, diagnostic and reference tests, results, descriptions of the patient sample, and future applications. Sample sizes were heterogeneous, both for size as well as for tumor type. Only one author studied a single type of cancer with FAPI tracers. Progression of disease was the most common outcome, and no relevant collateral effects were noted. Although FAPI theranostics is still in its infancy and lacks solid grounds to be brought into clinical practice, it does not show any collateral effects that prohibit administration to patients, thus far, and has good tolerability profiles. Full article

(This article belongs to the Special Issue Targeted Treatments in Cancer)

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