Research progress on genome-guided precision oncology and development ideas of antitumor Chinese medicine / 中国中药杂志

Genome-guided oncology refers to a new treatment concept that transcends histological classification and pathological ty-ping and uses drugs according to the genetic characteristics of tumors. New drug development technology and clinical trial design based on this concept provide new ideas for the clinical application of precision oncology. The multi-component and multi-target characteristics of Chinese medicine provide rich resources for the development of tumor-targeting drugs from natural products, and the design of the master protocol trial aiming at the characteristics of precision oncology supports the rapid clinical screening of effective tumor-targeting drugs. The emergence of the synthetic lethality strategy breaks through the bottleneck that the drug can only target the oncogene but cannot do anything to the tumor suppressor gene with the loss-of-function mutation in the past. With the rapid development of high-throughput sequencing technology, the cost of sequencing is also decreasing. For the development of tumor-targeting drugs, how to keep up with the update speed of target information is a difficult problem of concern. Based on the integration of innovative ideas and me-thods of precision oncology, network pharmacology, and synthetic lethality strategy on synthetic lethal interaction network of antitumor Chinese medicine compatibility formula design, and the combination of improvement of innovative clinical trial methods, such as master protocol trial, basket trial, and umbrella trial, unique advantages of Chinese medicine are expected to be exerted beyond the antibody-based drugs and small molecule-based drugs and corresponding targeted drugs are potentially developed for clinical application.

Mechanisms of histone methylation and acetylation modifying enzymes in ovarian cancer and therapeutic advances / 中国临床药理学与治疗学

Ovarian cancer is the most malignant gynecologic malignancy. In recent years, histone modifying enzymes (HMEs) have been widely studied as an important part of epigenetic modifi-cations in ovarian cancer. Histone modifying enzymes, including histone methyltransferases and demethylases, histone acetyltransferases and deacetylases, play an important role in the prolif-eration and migration of ovarian cancer cells by modifying histone and non-histone proteins, and can regulate the development of chemoresistance. Inhibitors of various histone modifying enzymes play good anti-tumor effects in ovarian cancer by promoting cell growth arrest and apoptosis, inhibi¬ting tumor cell invasion, and increasing chemo¬therapy sensitivity, and are expected to be a new strategy for precision treatment of ovarian cancer. Therefore, this paper will review the mechanism of action and therapeutic potential of histone modifying enzymes involved in methylation and acetylation processes in ovarian cancer.

Clinical value of gene detection in metastatic prostate cancer / 中华泌尿外科杂志

The incidence of prostate cancer has increased over the past several years and it has become a major disease that seriously harms male health. Advanced prostate cancer is a heterogeneous disease with poor outcomes, the median overall survival of advanced prostate cancer usually less than two years. Clinical challenges include determining the optimal sequencing of systemic therapies and implementing biomarker-driven treatment approaches. The emergence of precision treatment has brought about a diagnosis and treatment strategy based on molecular testing, which provides the possibility for the formulation of individualized treatment plans.

Glycoproteogenomics: Setting the Course for Next-generation Cancer Neoantigen Discovery for Cancer Vaccines / 基因组蛋白质组与生物信息学报·英文版

Molecular-assisted precision oncology gained tremendous ground with high-throughput next-generation sequencing (NGS), supported by robust bioinformatics. The quest for genomics-based cancer medicine set the foundations for improved patient stratification, while unveiling a wide array of neoantigens for immunotherapy. Upfront pre-clinical and clinical studies have successfully used tumor-specific peptides in vaccines with minimal off-target effects. However, the low mutational burden presented by many lesions challenges the generalization of these solutions, requiring the diversification of neoantigen sources. Oncoproteogenomics utilizing customized databases for protein annotation by mass spectrometry (MS) is a powerful tool toward this end. Expanding the concept toward exploring proteoforms originated from post-translational modifications (PTMs) will be decisive to improve molecular subtyping and provide potentially targetable functional nodes with increased cancer specificity. Walking through the path of systems biology, we highlight that alterations in protein glycosylation at the cell surface not only have functional impact on cancer progression and dissemination but also originate unique molecular fingerprints for targeted therapeutics. Moreover, we discuss the outstanding challenges required to accommodate glycoproteomics in oncoproteogenomics platforms. We envisage that such rationale may flag a rather neglected research field, generating novel paradigms for precision oncology and immunotherapy.

Molecular Imaging in Breast Cancer / 대한핵의학회잡지

Breast cancer (BC) is themost common cancer among females withmore than 2 million new cases diagnosed worldwide in 2018. Although the prognosis in the majority of cases in the early stages combined with appropriate treatment is positive, there are still about 30% of patients who will develop locoregional diseases and distant metastases. Molecular imaging is very important in the diagnosis, staging, follow-up, and radiotherapy planning. Additionally, it is useful in characterizing lesions, prognosis, and therapy response in BC patients. Nuclear medicine imaging modalities (SPECT and PET) are of indispensable importance in diagnosis (positron emission mammography), staging (sentinel lymph node detection), and follow-up with ¹⁸F-FDG and tumor characterization. Among many available PET tracers, the most commonly used are ¹⁸F-FLT, ¹⁸F-FES, ¹⁸F-FDHT, ⁶⁴Cu DOTA trastuzumab (bevacizumab), ⁶⁸Ga-PSMA, ⁶⁸Ga-RM2 (gastrin-releasing peptide receptor), ¹⁸F-fluorooctreotide (SSTR), and ⁶⁸Ga-TRAP (RGD)-3αvβ3-integrin. Molecular imaging helps in evaluation of tumor heterogeneity, allowing a shift from one-size-fits-all-approach to era of personalized medicine and precision oncology.

Applications of RNA Indexes for Precision Oncology in Breast Cancer / 基因组蛋白质组与生物信息学报·英文版

Precision oncology aims to offer the most appropriate treatments to cancer patients mainly based on their individual genetic information. Genomics has provided numerous valuable data on driver mutations and risk loci; however, it remains a formidable challenge to transform these data into therapeutic agents. Transcriptomics describes the multifarious expression patterns of both mRNAs and non-coding RNAs (ncRNAs), which facilitates the deciphering of genomic codes. In this review, we take breast cancer as an example to demonstrate the applications of these rich RNA resources in precision medicine exploration. These include the use of mRNA profiles in triple-negative breast cancer (TNBC) subtyping to inform corresponding candidate targeted therapies; current advancements and achievements of high-throughput RNA interference (RNAi) screening technologies in breast cancer; and microRNAs as functional signatures for defining cell identities and regulating the biological activities of breast cancer cells. We summarize the benefits of transcriptomic analyses in breast cancer management and propose that unscrambling the core signaling networks of cancer may be an important task of multiple-omic data integration for precision oncology.