The requirement of having multiple nanocarriers (NCs) and active agents for improved therapy, imaging, and controlled release of medications efficiently in one platform has made the creation of therapeutics and theragnostic nanodrug delivery systems a difficult task for present researchers. Multiple drug resistance (MDR), a high clearance rate, severe side effects, undesirable drug distribution to the specific site of liver cancer, and a low concentration of medication that reaches liver cancer cells are just a few of the drawbacks of traditional liver cancer chemotherapy. As a result, new techniques and NCs must be developed to transport the medication molecules targeted to the malignant hepatocytes in an acceptable number and duration inside the therapeutic window. Because of the great efficacy of drug loading or drug encapsulation efficiency, high cellular uptake, high drug release, and minimal adverse effects, therapeutics and theragnostic systems have benefits over conventional chemotherapy. These NCs have a high drug accumulation rate in tumours while causing minimal toxicity in healthy tissues. This study focuses on current research on NC-based therapies and theragnostic drug delivery systems, omitting nanotechnology's negative consequences in the field of drug delivery systems. Clinical advancements of theragnostic NCs for liver cancer, on the other hand, are not covered in this article. Only the most current breakthroughs in NC-based drug delivery systems for liver cancer therapy and diagnosis are discussed in this study. This review will not go over the detrimental effects of individual NCs in the medication delivery system.

Despite the advantages of nanoscale drug delivery systems, traditional nanoparticles often encounter challenges such as detection and elimination by the immune system. To circumvent these limitations, scientists have created biomimetic nanoparticles that extend circulation time, decrease clearance rates, and optimize drug delivery. The integration of cell membranes onto nanoparticle surfaces yields Cell Membrane-coated Nanoparticles (CMNPs) that exhibit behavior akin to actual cells while offering superior structural robustness and stability. A variety of cell membranes, including those of red blood cells, white blood cells, and cancer cells, lend unique properties and targeting capabilities to CMNPs. This review outlines the diagnostic and therapeutic roles of CMNP-based drug delivery systems in oncology and contemplates their possible clinical impact.

Breast cancer, as a malignant tumor with easy metastasis and poor prognosis, threatens the health of women around the world. Increasing studies have shown that the Bcl-2 family of apoptosis-related proteins is often expressed abnormally in breast cancer. The Bcl-2 homology 3 (BH3) mimetic peptide can bind and neutralize Bcl-2, preventing its binding to the apoptosis "effector" proteins Bak and Bax, thereby promoting the apoptosis process. However, there is a lack of effective intracellular delivery system for BH3 to exert its biological activity. Therefore, this study utilized an activatable supercharged polypeptide (ASCP) tumor-targeted delivery platform based on pH and protease response to achieve the targeted release of BH3 at the tumor site. Ultimately, intracellular delivery of BH3 was achieved and induced apoptosis of breast tumor cells, preventing the development of breast cancer.

With the improvement of people's living standards and the increasing emphasis on health, new and higher demands are also placed on the medical industry. The diagnosis and treatment methods combining artificial intelligence and medicine are bound to receive more and more attention and promotion. At present, drug design is stepping into the era of artificial intelligence, and academia and industry are actively applying artificial intelligence technology to all aspects of drug research and development, including drug screening, molecular characterization, drug activity and druggability optimization, chemical reaction design, etc. Relying on the big data information of millions of patients, the artificial intelligence system can quickly and accurately mine and screen out suitable drugs. Through computer simulations, artificial intelligence can make predictions about drug activity, safety, and side effects, and find the best drug that matches the disease. This technology will shorten the drug development cycle, reduce the cost of new drugs and improve the success rate of new drug development.

Cancer chemotherapy is generally associated with many severe adverse effects. Many cancer studies are currently focused on repurposing conventional non-toxic anti-parasite drugs for cancer treatment. Since cancer cells and parasites have many features in common, some anti-parasite drugs such as benzimidazoles have been recently found to possess the anti-cancer activity. Benzimidazoles act against cancer by inhibiting tubulin polymerization, inducing cancer cell apoptosis, arresting cell cycle and over-generating reactive oxygen specimen. In this review, we summarize the anticancer features of these drugs in recent investigations, lead to reconsideration of benzimidazoles as a family of anti-cancer chemotherapeutics with non-toxicity or low toxicity to the normal cells and tissues. We particularly highlight the recent progresses using nanoformulations for enhanced cancer therapy and provide our prospects in the future research.

Metadherin (MTDH), also known as LYRIC or AEG-1, is an oncogene that enhances tumor progression, metastasis, drug resistance, and immune escape in various cancers by modulating multiple oncogenic pathways, including NF-κB, PI3K/AKT, Wnt/β-catenin, MAPK, and AMPK. Due to the unknown of the complete structure of MTDH, the deep mechanisms of MTDH and selective inhibitors targeting MTDH remain to be explored. The Protein-Protein interaction (PPI) with the Staphylococcal nuclease domain containing 1 (SND1) is a crucial mechanism underlying the function of MTDH. Current studies have demonstrated that inhibitors, including antisense oligonucleotides, peptides, and small molecules targeting MTDH or MTDH-SND1 interactions, provide novel strategies to inhibit the oncogenetic effects of MTDH. This review summarizes and discusses the structure, function, and regulation of MTDH in cancers, providing the potential therapeutic perspectives of MTDH or MTDH-SND1 PPI for drug discovery.

Approximately 28 million individuals in the United States face the risk of developing precancerous colonic adenomas (polyps) and potentially progressing to colorectal cancer (CRC). While a promising strategy for CRC prevention involves pharmacological intervention, such as cancer chemoprevention or interception, currently, there are no FDA-approved drugs capable of preventing the formation or progression of adenomas to adenocarcinoma. Numerous clinical, epidemiological, and preclinical studies have offered compelling evidence supporting the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in CRC chemoprevention. However, the prolonged use of NSAIDs is not FDA-approved due to potential life-threatening toxicities resulting from cyclooxygenase (COX) inhibition and the depletion of physiological prostaglandins. Despite indications that the COX inhibitory activity of NSAIDs may not be essential for their antineoplastic effects, the absence of a well-defined target impeded the development of derivatives that do not inhibit COX. Earlier research suggests that the inhibition of cyclic guanosine monophosphate phosphodiesterase (cGMP PDE) may be responsible, at least in part, for the antineoplastic activity of the NSAID sulindac. This could potentially offer a novel target for CRC chemoprevention. To identify the cGMP PDE isozyme(s) contributing to the antineoplastic activity of sulindac, we synthesized a chemically diverse library of over 1500 compounds, all sharing the indene scaffold of sulindac. Subsequently, we screened these compounds for their impact on cancer cell growth and PDE inhibitory activity. From this screening, a series of lead compounds emerged. These compounds lacked COX-1 and COX-2 inhibitory activity, surpassing sulindac in potency to inhibit CRC cell growth. Importantly, they demonstrated greater selectivity by not affecting normal cell growth. Through chemical optimization, we identified several development candidates that selectively inhibit PDE5 and/or PDE10. These compounds activate cGMP/PKG signaling, suppressing Wnt/β-catenin transcription. This action counters the growth advantages resulting from APC or CTNNB1 mutations, which are responsible for most human CRCs. This review delves into the scientific literature supporting PDE5 and/or PDE10 as potential targets for CRC chemoprevention or interception. Our findings suggest a promising avenue for developing drugs that may effectively intervene in the progression of colorectal cancer, offering hope for improved preventive strategies in the future.

Transition metal sulfides/transition metal phosphides (TMS/TMP) has shown great potential in cancer diagnosis and treatment due to its unique structural, optical, acoustic and magnetic properties. TMS/TMP can be formed from sulfur/phosphorus source and metal into binary compounds, or from the interaction of hydrogen sulfide (or hydrogen sulfuric acid) with metal oxides or hydroxides. It has a series of unique properties, such as high conductivity, metalloid properties, a variety of valence states and adjustable structure and so on. These advantages make it have great potential in biomedical applications, such as diagnostic imaging, disease therapy and drug/gene delivery. This review presents the latest research progress of TMS/TMP on tumor imaging, diagnosis and treatment. Here, we first illustrate the synthesis approaches and surface modification of TMS/TMP. Then, its emerging applications in tumor diagnosis and therapy are highlighted. Moreover, the challenges of TMS/TMP-mediated diagnosis/treat are provided and the prospective for this field are discussed.

Cancer, a pervasive threat to human health, presents formidable challenges to traditional treatment approaches. Tumor immunotherapy has emerged as a promising strategy for combating malignancies by bolstering the body's immune response to thwart tumor metastasis and recurrence. Nonetheless, the intricacies of tumors, patient heterogeneity, and the presence of tumor-immunosuppressive microenvironments have limited the overall efficacy of immunotherapy, achieving only approximately a 20% success rate. In recent years, nanomaterials have garnered increasing attention in the realm of tumor immunotherapy due to their inherent advantages, such as excellent biocompatibility, precise targeting, and controlled drug release. Nanomaterials empower immunostimulatory molecules and therapeutic agents with the ability to specifically target tumors, amplify drug accumulation at tumor sites, facilitate local immune modulation, alleviate immunosuppressive microenvironments, and thereby enhance the effectiveness of tumor immunotherapy. This review provides an overview of the current state of immunotherapy and offers insights into the ongoing research progress surrounding various nanomaterials aimed at augmenting the efficacy of immunotherapy.

Adenosine alterations to RNA, which are largely determined by RNA modification writers (RMWs), are critical for cancer growth and progression. These RMWs can catalyze different types of adenosine modifications, such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), alternative polyadenylation (APA), and adenosine-to-inosine (A-to-I) RNA editing. These modifications have profound effects on gene expression and function, such as immune response, cell development. Despite this, the clinical effects of RMW interactive genes on these cancers remain largely unclear. A comprehensive analysis of the clinical impact of these epigenetic regulators in pan-cancer requires further comprehensive exploration. Here, we systematically profiled the molecular and clinical characteristics of 26 RMWs across 33 cancer types using multi-omics datasets and validated the expression level of some RMWs in various cancer lines. Our findings indicated that a majority of RMWs exhibited high expression in diverse cancer types, and this expression was found to be significantly associated with poor patient outcomes. In the genetic alterations, the amplification and mutation of RMWs were the dominant alteration events. Consequently, the RNA Modification Writer Score (RMW score) was established as a means to assess the risk of RMWs in pan-cancer. We found that 27 of 33 cancers had significantly higher scores compared with normal tissues, and it was significantly correlated with prognosis. We also evaluated their impact on the tumor microenvironment and the response to immunotherapy and targeted therapy. These findings verified the important role of RMWs in different aspects of cancer biology, and provided biomarkers and personalized therapeutic targets for cancer.

The paramount prerequisite for effective anti-cancer drugs is their ability to eradicate malignant cells while sparing non-cancer cells. The divergence in properties between malignant and non-cancer cells establishes a "therapeutic window," a critical consideration for achieving desirable treatment outcomes. Central to this is the imperative of a cancer drug's "selectivity and specificity." Taxanes, a pivotal class of successful anti-cancer drugs, continue to serve as the linchpin of cancer treatment due to their efficacy across a spectrum of cancer types. Operating as broad-spectrum chemotherapeutic agents, taxanes exert cytotoxic effects on proliferative cancer cells by binding to and stabilizing microtubules, disrupting mitosis, inducing mitotic catastrophe, and resulting in cell death. The distinct proliferative nature of cancer cells, as opposed to less proliferative non-cancer cells, affords taxanes a measure of specificity and selectivity. Nevertheless, sporadic yet recurring evidence suggests that taxanes also operate through non-mitotic mechanisms. Taxanes' binding and stabilization of microtubules lead to micronucleation and subsequent cell death, impacting both mitotic and non-mitotic cells. Recent discoveries indicate that the flexible and weakened nuclear envelope of malignant cells renders them sensitive to taxane-mediated micronucleation and cell death during various phases of the cell cycle. Conversely, non-cancerous cells typically exhibit a more robust and sturdy nuclear envelope, rendering them more tolerant to taxane-induced nuclear envelope fragmentation and subsequent micronucleation and cell death. The expression levels of nuclear envelope structural proteins, particularly Lamin A/C, emerge as indicators of taxane sensitivity. This evolving understanding underscores that nuclear envelope malleability, in conjunction with a high proliferation rate, is a pivotal determinant of taxane specificity and selectivity against malignant cells. These insights necessitate reconsidering oncological strategies to augment taxane efficacy, overcome resistance, and mitigate side effects.

Protein S-nitrosylation (SNO), emerging as an important posttranslational modification, involves covalent addition of nitric oxide (NO) to the sulfur atom of cysteine in proteins. Accumulated evidence suggests that protein SNO plays crucial roles in pathophysiological mechanisms in cancer, which is attracting great attention. However, there are still controversies about whether S-nitrosylated proteins act as oncogenic proteins or tumor suppressors in cancer. In this review, we provide an overview of the early and latest evidence regarding the underlying mechanism and dual roles of SNO in cancer, in an effort to clarify its contribution in tumor progression. It has been well established that S-nitrosylated proteins restrain tumor progression in several types of cancer, while they have exhibited activities in promoting cell proliferation and inhibiting apoptosis in some other kinds of cancer. Interestingly, emerging evidence also has highlighted both its anti-cancer and pro-tumorigenic roles in several other cancer diseases. Finally, current limitations and future research prospects are presented. The overview of targeting SNO in cancer will provide new opportunities for drug development through in-depth exploration of SNO-mediated signaling pathways.

Although docetaxel treatment yields a high survival rate for prostate cancer (PCa), resistance eventually develops in many patients. Understanding the underlying mechanisms of docetaxel resistance is essential for improving treatment strategies. Cytokines, which play a role in cell signaling and immune responses, have been implicated in drug resistance mechanisms. The study revealed that interleukin-8 (IL-8) was consistently overexpressed in both docetaxel-resistant PCa cell lines. Thus, the expression levels of cytokines released from docetaxel-sensitive (PC-3- and DU-145) and resistant (PC-3/R-DU-145/R) PCa cells were compared. IL-8 was found to be commonly expressed in resistant cell lines. This finding led to the hypothesis that IL-8 could play a key role in mediating PCa cell resistance to docetaxel. IL-8 siRNA treatment increased docetaxel sensitivity in both resistant cells. To demonstrate the mechanism of IL-8-related resistance, MDR1 expression was evaluated. After IL-8 siRNA treatment MDR1 expression was reduced in both resistant cells suggesting that IL-8 regulates the docetaxel resistance of PCa cells via modulation of multidrug resistance 1 (MDR1). By expanding the knowledge of the cytokines and their effect mechanisms, novel approaches can be developed for the treatment of docetaxel-resistant prostate cancer. Further investigations into the role of IL-8 in docetaxel resistance could offer valuable insights into the development of effective treatment strategies for PCa patients.