Natural products, with remarkable chemical diversity, have been extensively investigated for their anticancer potential for more than a half-century. The collective efforts of the community have ...achieved the tremendous advancements, bringing natural products to clinical use and discovering new therapeutic opportunities, yet the challenges remain ahead. With remarkable changes in the landscape of cancer therapy and growing role of cutting-edge technologies, we may have come to a crossroads to revisit the strategies to understand nature products and to explore their therapeutic utility. This review summarizes the key advancements in nature product-centered cancer research and calls for the implementation of systematic approaches, new pharmacological models, and exploration of emerging directions to revitalize natural products search in cancer therapy.
Given the successful identification of epidermal growth factor receptor EGFR T790M, the third-generation EGFR tyrosine kinase inhibitor (TKI), osimertinib (OSI, AZD9291), was developed to target EGFR ...T790M mutation. OSI was approved for the treatment of patients with non-small cell lung cancer (NSCLC) harboring EGFR T790M mutation. However, the disease would progress after the patient received OSI treatment for approximately 10 months. Resistance mechanisms to OSI, such as additional mutation of EGFR and alternative kinase activation, were recently identified, and some novel therapeutic strategies were proposed to overcome OSI resistance. In this review, the resistance mechanisms and therapeutic strategies for OSI-resistant NSCLC were summarized to direct further use of OSI and aid in the development of novel drugs or strategies for OSI-resistant NSCLC.
•Both EGFR-dependent and -independent manners contribute to the resistant mechanisms.•Re-biopsy to study the resistance mechanisms at the time of progression is required.•Immunotherapy might be used for treating a sub-set of OSI-resistant NSCLC.•More research is needed for treating NSCLC harboring naive EGFR mutation with OSI.
Chemotherapy is the standard internal medical treatment for cancer. However, the resistance of cancer cells to nearly all kinds of chemotherapeutic drugs and targeted drugs has become prevalent, and ...approximately 80–90% of deaths in cancer patients are directly or indirectly attributed to drug resistance. The progress of new drug research and development has also been impeded by the occurrence of drug resistance, which has emerged as a considerable challenge in cancer therapy. Fortunately, natural products with diverse chemical structures and pharmacological effects serve as effective substances against drug resistance. Since the discovery of a series of drug‐resistant proteins, drug‐efflux inhibition has been applied as the primary strategy to overcome drug resistance by maintaining the intracellular concentrations of chemotherapeutic drugs. Nonapoptotic cell death is considered an alternative strategy because most cases of drug resistance result in evasion and insensitivity to apoptosis. In this concise review, we summarize two strategies using natural products against drug resistance.
Perturbo is a software package for first-principles calculations of charge transport and ultrafast carrier dynamics in materials. The current version focuses on electron–phonon interactions and can ...compute phonon-limited transport properties such as the conductivity, carrier mobility and Seebeck coefficient. It can also simulate the ultrafast nonequilibrium electron dynamics in the presence of electron–phonon scattering. Perturbo uses results from density functional theory and density functional perturbation theory calculations as input, and employs Wannier interpolation to reduce the computational cost. It supports norm-conserving and ultrasoft pseudopotentials, spin–orbit coupling, and polar electron–phonon interactions for bulk and 2D materials. Hybrid MPI plus OpenMP parallelization is implemented to enable efficient calculations on large systems (up to at least 50 atoms) using high-performance computing. Taken together, Perturbo provides efficient and broadly applicable ab initio tools to investigate electron–phonon interactions and carrier dynamics quantitatively in metals, semiconductors, insulators, and 2D materials.
Program Title:Perturbo
CPC Library link to program files:https://doi.org/10.17632/34m2p6v79t.1
Developer’s repository link:https://perturbo-code.github.io
Licensing provisions: GNU General Public Licence 3.0
Programming language:Fortran, Python
External routines/libraries:LAPACK, HDF5, MPI, OpenMP, FFTW, Quantum-ESPRESSO, Wannier90
Nature of problem: Computing transport properties from first-principles in materials, including the electrical conductivity, carrier mobility and Seebeck coefficient; Simulating ultrafast nonequilibrium electron dynamics, such as the relaxation of excited carriers via interactions with phonons.
Solution method: We implement the first-principles Boltzmann transport equation, which employs materials properties such as the electronic structure, lattice dynamics, and electron–phonon collision terms computed with density functional theory and density functional perturbation theory. The Boltzmann transport equation is solved numerically to compute charge transport and simulate ultrafast carrier dynamics. Wannier interpolation is employed to reduce the computational cost.
Additional comments: Hybrid MPI plus OpenMP parallelization is implemented to run large calculations and take advantage of high-performance computing. Most results are output to HDF5 file format, which is portable and convenient for post-processing using high-level languages such as Python and Julia.
Summarizing the status of drugs in the market and examining the trend of drug research and development is important in drug discovery. In this study, we compared the drug targets and the market sales ...of the new molecular entities approved by the U.S. Food and Drug Administration from January 2000 to December 2009. Two networks, namely, the target-target and drug-drug networks, have been set up using the network analysis tools. The multi-target drugs have much more potential, as shown by the network visualization and the market trends. We discussed the possible reasons and proposed the rational strategies for drug research and development in the future.
Summary
The Orchidaceae is of economic and ecological importance and constitutes ˜10% of all seed plant species. Here, we report a genome physical map for Cymbidium sinense, a well‐known species ...belonging to genus Cymbidium that has thousands of natural variation varieties of flower organs, flower and leaf colours and also referred as the King of Fragrance, which make it arose into a unique cultural symbol in China. The high‐quality chromosome‐scale genome assembly was 3.52 Gb in size, 29 638 protein‐coding genes were predicted, and evidence for whole‐genome duplication shared with other orchids was provided. Marked amplification of cytochrome‐ and photosystem‐related genes was observed, which was consistent with the shade tolerance and dark green leaves of C. sinense. Extensive duplication of MADS‐box genes, and the resulting subfunctional and expressional differentiation, was associated with regulation of species‐specific flower traits, including wild‐type and mutant‐type floral patterning, seasonal flowering and ecological adaption. CsSEP4 was originally found to positively regulate gynostemium development. The CsSVP genes and their interaction proteins CsAP1 and CsSOC1 were significantly expanded and involved in the regulation of low‐temperature‐dependent flowering. Important genetic clues to the colourful leaf traits, purple‐black flowers and volatile trait in C. sinense were also found. The results provide new insights into the molecular mechanisms of important phenotypic traits of Cymbidium and its evolution and serve as a powerful platform for future evolutionary studies and molecular breeding of orchids.
An electrical-thermal co-simulation based on the finite element method is presented for analysis of high-power RF/microwave circuits. The co-simulation integrates a full-wave electromagnetic analysis ...and a transient thermal analysis through an iterative scheme, and is devised for the design and analysis of RF/microwave circuits operated at high frequencies and high power levels. To enhance the efficiency in solving large-scale problems, a domain decomposition scheme called the finite element tearing and interconnecting and an adaptive time-stepping scheme based on the algorithm of proportional-integral-derivative control are incorporated into the co-simulation. Temperature stability analysis is performed with the proposed co-simulation for a matching network in high-power RF amplifiers and for a substrate integrated waveguide filter.
Cancer is still presenting a serious threat to human health worldwide. The understanding of the complex biology of cancer and the development of oncotherapy have led to increasing treatment ...approaches such as targeted therapy and immunotherapy. Chinese medicinal herbs have attracted considerable attention due to their potential anticancer effects. Some natural products or formulae from Chinese medicinal herbs with directly or indirectly anticancer effects have been reported. In this article, we summarized the current progression on development of anticancer drugs from Chinese medicinal herbs, toward providing ideas for further development and application of Chinese medicinal herbs in cancer therapy.
As an anthracycline antibiotic, doxorubicin (DOX) is one of the most potent and widely used chemotherapeutic agents for various types of solid tumors. Unfortunately, clinical application of this drug ...results in severe side effects of cardiotoxicity.
We aim to review the research focused on elimination or reduction of DOX cardiotoxicity without affecting its anticancer efficacy by natural products.
This study is based on pertinent papers that were retrieved by a selective search using relevant keywords in PubMed and ScienceDirect. The literature mainly focusing on natural products and herb extracts with therapeutic efficacies against experimental models both in vitro and in vivo was identified.
Current evidence revealed that multiple molecules and signaling pathways, such as oxidative stress, iron metabolism, and inflammation, are associated with DOX-induced cardiotoxicity. Based on these knowledge, various strategies were proposed, and thousands of compounds were screened. A number of natural products and herb extracts demonstrated potency in limiting DOX cardiotoxicity toward cultured cells and experimental animal models.
Though a panel of natural products and herb extracts demonstrate protective effects on DOX-induced cardiotoxicity in cells and animal models, their therapeutic potentials for clinical needs further investigation.
•The small-molecule inhibitors targeting CD47/SIRPα axis, a promising phagocytosis checkpoint in cancer therapy, are reviewed for the first time.•In addition to targeting the interaction of ...CD47/SIRPα, compounds regulating CD47 at transcriptional, translational and posttranslational levels are summarized.•Challenges followed by the corresponding strategies are proposed for further development of small-molecule inhibitors targeting CD47/SIRPα axis.
Immunotherapy has become an indispensable part of cancer treatment. A pivotal phagocytosis checkpoint, named cluster of differentiation 47 (CD47), which functions as ‘don’t eat me’ signal to protect cells from phagocytosis upon interaction with signal regulatory protein alpha (SIRPα) on macrophages, has recently attracted much attention. Numerous antibodies targeting the CD47/SIRPα axis have shown encouraging efficacy in clinical trials. Meanwhile, studies on small-molecule inhibitors that interfere with CD47/SIRPα interaction or regulate CD47 expression are also in full swing. In this review, we summarize the small-molecule inhibitors interrupting the binding of CD47/SIRPα and regulating CD47 at the transcriptional, translational, and post-translational modification (PTM) levels. We provide perspectives and strategies for targeting the CD47/SIRPα phagocytosis checkpoint.
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