Frontiers in Oncology

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ISSN / EISSN : 2234-943X / 2234-943X
Current Publisher: Frontiers Media SA (10.3389)
Total articles ≅ 8,996
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Kun Chen, Kehua Jiang, Lannan Tang, Xiaolong Chen, Jianxin Hu,
Published: 12 May 2021
Frontiers in Oncology, Volume 11; doi:10.3389/fonc.2021.647110

Abstract:
The overall aging of the world population has contributed to the continuous upward trend in the incidence of prostate cancer (PC). Trials on PC therapy have been extensively performed, but no study has analyzed the overall trends and characteristics of these trials, especially for those carried out in China. This study aimed to provide insights on the future direction of drug development in PC, thus supplying essential supportive data for stakeholders, including researchers, patients, investors, clinicians, and pharmaceutical industry. The details of the clinical trials of drug therapies for PC during January 1, 2010, to January 1, 2020, were collected from Pharmaprojects. A total of 463 clinical trials on different therapies with 132 different drugs were completed. The long-acting endocrine therapy with few side effects, radiotherapy combined with immune checkpoint inhibitors, gene-targeted chemotherapeutics, and novel immunotherapeutic products changed the concept of PC treatment. In mainland China, 31 trials with 19 drugs have been completed in the 10 assessment years. China has initiated a few trials investigating a limited number of drug targets, centered in a markedly uneven geographical distribution of leading clinical trial units; hence, the development of PC drugs has a long way to go. Given the large patient pool, China deserves widespread attention for PC drug research and development. These findings might have a significant impact on scientific research and industrial investment.
Tetsuya Yamamoto, , Koji Hatano, Atsunari Kawashima, Takeshi Ujike, Shinichiro Fukuhara, Hiroshi Kiuchi, Ryoichi Imamura, Naokazu Ibuki, Kazuma Kiyotani, et al.
Published: 12 May 2021
Frontiers in Oncology, Volume 11; doi:10.3389/fonc.2021.691996

Abstract:
Tuberous sclerosis complex is a genetic disorder characterized by facial angiofibromas, intellectual disability, epilepsy, and tumor formation in multiple organs, including the kidney. Renal cell carcinoma occurs in 2%–4% of patients with tuberous sclerosis complex, often developing multiply and bilaterally. Renal cell carcinoma associated with this genetic disorder may include complex tumor heterogeneity caused by the spatially different mutational landscape. Herein, we report the case of a female patient with tuberous sclerosis complex who developed multiple renal tumors. A 44-year-old female patient with tuberous sclerosis complex developed three different histological types of tumor—angiomyolipoma, clear cell renal cell carcinoma, and papillary renal cell carcinoma—in the left kidney at first renal cell carcinoma recurrence. The papillary renal cell carcinoma was morphologically atypical, indicating that its occurrence was associated with the genetic disorder. Furthermore, whole-exome sequencing revealed distinct patterns of somatic mutation in the three tumor types, and the atypical papillary renal cell carcinoma possessed a different mutational landscape than that of typical papillary renal cell carcinomas. Our findings indicate that tumors associated with tuberous sclerosis complex may be diagnosed with careful pathological examination. Furthermore, somatic mutation profiles of these tumors revealed their unique features, providing important information for further understanding the mechanism of multiple tumor development in patients with tuberous sclerosis complex.
Christian Bäumer, Sandija Plaude, Dalia Ahmad Khalil, Dirk Geismar, Paul-Heinz Kramer, Kevin Kröninger, Christian Nitsch, Jörg Wulff, Beate Timmermann
Published: 12 May 2021
Frontiers in Oncology, Volume 11; doi:10.3389/fonc.2021.599018

Abstract:
Proton therapy makes use of the favorable depth-dose distribution with its characteristic Bragg peak to spare normal tissue distal of the target volume. A steep dose gradient would be desired in lateral dimensions, too. The widespread spot scanning delivery technique is based, however, on pencil-beams with in-air spot full-widths-at-half-maximum of typically 1 cm or more. This hampers the sparing of organs-at-risk if small-scale structures adjacent to the target volume are concerned. The trimming of spot scanning fields with collimating apertures constitutes a simple measure to increase the transversal dose gradient. The current study describes the clinical implementation of brass apertures in conjunction with the pencil-beam scanning delivery mode at a horizontal, clinical treatment head based on commercial hardware and software components. Furthermore, clinical cases, which comprised craniopharyngiomas, re-irradiations and ocular tumors, were evaluated. The dosimetric benefits of 31 treatment plans using apertures were compared to the corresponding plans without aperture. Furthermore, an overview of the radiation protection aspects is given. Regarding the results, robust optimization considering range and setup uncertainties was combined with apertures. The treatment plan optimizations followed a single-field uniform dose or a restricted multi-field optimization approach. Robustness evaluation was expanded to account for possible deviations of the center of the pencil-beam delivery and the mechanical center of the aperture holder. Supplementary apertures improved the conformity index on average by 15.3%. The volume of the dose gradient surrounding the PTV (evaluated between 80 and 20% dose levels) was decreased on average by 17.6%. The mean dose of the hippocampi could be reduced on average by 2.9 GyRBE. In particular cases the apertures facilitated a sparing of an organ-at-risk, e.g. the eye lens or the brainstem. For six craniopharyngioma cases the inclusion of apertures led to a reduction of the mean dose of 1.5 GyRBE (13%) for the brain and 3.1 GyRBE (16%) for the hippocampi.
Yan Yan, Xiao Cheng, Lin Li, Rumeng Zhang, Yong Zhu, Zhengsheng Wu, Keshuo Ding
Published: 12 May 2021
Frontiers in Oncology, Volume 11; doi:10.3389/fonc.2021.669393

Abstract:
Breast cancer is the most common malignant cancer in women worldwide, especially in developing countries. Herceptin is a monoclonal antibody with an antitumor effect in HER2-positive breast cancer. However, the large molecular weight of Herceptin limited its employment. In this study, we constructed and screened HER2-nanobody and verified its tumor-suppressive effect in HER2-positive breast cancer cells. HER2-nanobody was established, filtrated, purified, and was demonstrated to inhibit cell total number, viability, colony formation and mitosis, and promote cell apoptosis in HER2-positive breast cancer cells in vitro. Treated with HER2-nanobody, tumor growth was significantly inhibited by both intratumor injection and tail intravenous injection in vivo. The phosphorylation of ERK and AKT was restrained by HER2-nanobody in HER2-positive breast cancer cells. RAS-RAF-MAPK and PI3K-AKT-mTOR are two important pathways involved in HER2. It was credible for HER2-nanobody to play the tumor suppressive role by inhibiting the phosphorylation of ERK and AKT. Therefore, HER2-nanobody could be employed as a small molecular antibody to suppress HER2-positive breast cancer.
Miaoyan Wei, Bingxin Gu, Shaoli Song, Bo Zhang, Wei Wang, Jin Xu, ,
Published: 12 May 2021
Frontiers in Oncology, Volume 11; doi:10.3389/fonc.2021.650266

Abstract:
Objective Despite the heterogeneous biology of pancreatic cancer, similar surveillance schemas have been used. Identifying the high recurrence risk population and conducting prompt intervention may improve prognosis and prolong overall survival. Methods One hundred fifty-six resectable pancreatic cancer patients who had undergone 18F-FDG PET/CT from January 2013 to December 2018 were retrospectively reviewed. The patients were categorized into a training cohort (n = 109) and a validation cohort (n = 47). LIFEx software was used to extract radiomic features from PET/CT. The risk stratification system was based on predictive factors for recurrence, and the index of prediction accuracy was used to reflect both the discrimination and calibration. Results Overall, seven risk factors comprising the rad-score and clinical variables that were significantly correlated with relapse were incorporated into the final risk stratification system. The 1-year recurrence-free survival differed significantly among the low-, intermediate-, and high-risk groups (85.5, 24.0, and 9.1%, respectively; p < 0.0001). The C-index of the risk stratification system in the development cohort was 0.890 (95% CI, 0.835–0.945). Conclusion The 18F-FDG PET/CT-based radiomic features and clinicopathological factors demonstrated good performance in predicting recurrence after pancreatectomy in pancreatic cancer patients, providing a strong recommendation for an adequate adjuvant therapy course in all patients. The high-risk recurrence population should proceed with closer follow-up in a clinical setting.
Xiaojie Wang, Yarui Dai, Yina Zhao, Meichuan Li, Jialu Zhang, Yunzhe Ci, Huan Wang,
Published: 12 May 2021
Frontiers in Oncology, Volume 11; doi:10.3389/fonc.2021.665105

Abstract:
Gastric cancer is one of the most fatal diseases around the world. However, the mechanism of the development of gastric cancer is still not clarified. In addition, the anticancer drugs have cytotoxicity with different degrees. AnnexinA5, a member of the annexin family, has a great binding ability with the membrane phospholipid in a calcium dependent manner and is involved in the development of various cancers. This study aims to explore the influence of annexinA5 on human gastric cancer cells and whether it has the potential to be an auxiliary treatment to gastric cancer. In this study, the role of annexinA5 was detected from both the endogenous and the exogenous aspects on the gastric cancer cell lines MGC-803 and MKN-45. The cells were divided into a knockdown group in which RNA interference technique was used to suppress annexinA5 expression and a protein-supplementing group in which annexinA5 protein was added in the culture supernatant. After the suppression ratio of RNA interference was determined and the IC50 of annexinA5 protein was decided respectively, the cells’ proliferation was detected by MTT assay, colony formation assay, and the expression of PCNA. FCM assay and PI staining methods were applied to test cell apoptosis and necrosis. To investigate whether ANXA5 influence cell metastasis, wound healing assay and transwell assay were employed. To further detect the mechanism of annexinA5 action, the signal pathway was examined with Western Blot method. When ANXA5 gene was knocked down, cell proliferation and metastasis were promoted, while cell apoptosis was suppressed. On the other hand, after the annexinA5 protein was applied to the gastric cancer cells, cell proliferation and metastasis were inhibited, while cell apoptosis and necrosis were promoted. AnnexinA5 played its role via ERK signal pathway. ANXA5 acted as tumor suppressor gene in the gastric cancer by suppressing ERK signal pathway and has the potentiality to be an auxiliary anticancer agent.
, Syuzo Kaneko, Ken Takasawa, Hidenori Machino, Satoshi Takahashi, Norio Shinkai, Ryo Shimoyama, Masaaki Komatsu, Ryuji Hamamoto
Published: 12 May 2021
Frontiers in Oncology, Volume 11; doi:10.3389/fonc.2021.666937

Abstract:
With the completion of the International Human Genome Project, we have entered what is known as the post-genome era, and efforts to apply genomic information to medicine have become more active. In particular, with the announcement of the Precision Medicine Initiative by U.S. President Barack Obama in his State of the Union address at the beginning of 2015, “precision medicine,” which aims to divide patients and potential patients into subgroups with respect to disease susceptibility, has become the focus of worldwide attention. The field of oncology is also actively adopting the precision oncology approach, which is based on molecular profiling, such as genomic information, to select the appropriate treatment. However, the current precision oncology is dominated by a method called targeted-gene panel (TGP), which uses next-generation sequencing (NGS) to analyze a limited number of specific cancer-related genes and suggest optimal treatments, but this method causes the problem that the number of patients who benefit from it is limited. In order to steadily develop precision oncology, it is necessary to integrate and analyze more detailed omics data, such as whole genome data and epigenome data. On the other hand, with the advancement of analysis technologies such as NGS, the amount of data obtained by omics analysis has become enormous, and artificial intelligence (AI) technologies, mainly machine learning (ML) technologies, are being actively used to make more efficient and accurate predictions. In this review, we will focus on whole genome sequencing (WGS) analysis and epigenome analysis, introduce the latest results of omics analysis using ML technologies for the development of precision oncology, and discuss the future prospects.
Brian Keller, Anna M. E. Bruynzeel, Chad Tang, Anand Swaminath, Linda Kerkmeijer,
Published: 11 May 2021
Frontiers in Oncology, Volume 11; doi:10.3389/fonc.2021.634830

Abstract:
Adaptive MR-guided radiotherapy (MRgRT) is a new treatment paradigm and its role as a non-invasive treatment option for renal cell carcinoma is evolving. The early clinical experience to date shows that real-time plan adaptation based on the daily MRI anatomy can lead to improved target coverage and normal tissue sparing. Continued technological innovations will further mitigate the challenges of organ motion and enable more advanced treatment adaptation, and potentially lead to enhanced oncologic outcomes and preservation of renal function. Future applications look promising to make a positive clinical impact and further the personalization of radiotherapy in the management of renal cell carcinoma.
Judit Tőke, Zsuzsanna Jakab, Júlia Stark, Gergely Huszty, Péter Reismann,
Published: 11 May 2021
Frontiers in Oncology, Volume 11; doi:10.3389/fonc.2021.680853

Abstract:
Mitotane has been used for the treatment of adrenocortical cancer (ACC) for over 50 years. Despite its widespread use both in monotherapy and in combination with chemotherapeutics, our knowledge of its mechanism of action and therapeutic efficacy is scarce. The number of patients with advanced ACC who have achieved complete remission documented by detailed clinical data is below ten. We report a case of a 64-year-old woman with a non-functional ACC. Histological examination showed vascular invasion, Ki67 of 10% and a mitotic count of 3/10 high-power field. Immunohistochemistry revealed p53 positivity. Pathological TNM grade was reported as T2N0M0, ENSAT stage 2. Nine months after the initial diagnosis, re-staging CT revealed multiple peritoneal nodules, lymph node and kidney metastases confirmed by histologic examination. Mitotane monotherapy was started with a maintenance dose between 2.0 and 2.5 grams/day. Partial remission was established at six months. Subsequently, for another 12 months, each of the three-monthly CT scans confirmed complete remission. Nineteen months after the initiation of mitotane, an unexpected sudden death occurred. A detailed autopsy work-up, performed in the full awareness of oncological history, confirmed complete remission. The authors review the molecular biomarkers and clinical features reported as predictors of response to mitotane monotherapy.
Qinxian Zhao, Zhigang Cheng, Zhiyu Han, Fangyi Liu, Xiaoling Yu, Xianliang Tan, Bin Han, Jianping Dou, Jie Yu,
Published: 11 May 2021
Frontiers in Oncology, Volume 11; doi:10.3389/fonc.2021.638165

Abstract:
Purpose To compare the therapeutic outcomes between open surgical resection (OSR) and percutaneous microwave ablation (PMWA) for colorectal liver metastasis (CRLM) ≤3 cm. Methods In this retrospective study, 200 consecutive patients with 306 CRLMs were reviewed. Overall survival (OS), disease-free survival (DFS), local tumour progression (LTP), intrahepatic distant recurrence, and extrahepatic metastasis were analysed to compare the therapeutic efficacy. Cox proportional hazards regression analysis was used to identify the prognostic factors for OS and DFS. Major complications and postoperative hospital stay were also assessed. Result The 1-, 3-, and 5-year OS rates were 91.6%, 64.1%, and 46.3%, respectively, in the PMWA group and 89.7%, 62.4% and 44.7%, respectively, in the OSR group (P=0.839). The 1-, 3-, and 5-year DFS rates were 61.9%, 44.8%, and 41.3%, respectively, in the PMWA group and 58.1%, 24.4%, and 18.3%, respectively, in the OSR group (P =0.066). The two groups had comparable 5-year cumulative rates of intrahepatic distant recurrence (P=0.627) and extrahepatic metastasis (P=0.884). The 5-year cumulative LTP rate was lower in the OSR group than in the PMWA group (P=0.023). The rate of major complications was higher in the OSR group than in the PMWA group (P =0.025), and the length of hospital stay after treatment was shorter in the PMWA group (P<0.001). Conclusion There were no significant differences in OS or DFS between the two groups. PMWA was associated with increased LTP, fewer postoperative days and fewer major complications.
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