Conventional Cancer Therapies Research Articles

Microneedles for Efficient and Precise Drug Delivery in Cancer Therapy.

Cancer is the leading cause of death, acting as a global burden, severely impacting the patients' quality of life and affecting the world economy despite the expansion of cumulative advances in oncology. The current conventional therapies for cancer which involve long treatment duration and systemic exposure of drugs leads to premature degradation of drugs, a massive amount of pain, side effects, as well as the recurrence of the condition. There is also an urgent demand for personalized and precision-based medicine, especially after the recent pandemic, to avoid future delays in diagnosis or treatments for cancer patients as they are very essential in reducing the global mortality rate. Recently, microneedles which consist of a patch with tiny, micron-sized needles attached to it have been quite a sensation as an emerging technology for transdermal application to diagnose or treat various illnesses. The application of microneedles in cancer therapies is also being extensively studied as they offer a myriad of benefits, especially since microneedle patches offer a better treatment approach through self administration, painless treatment, and being an economically and environmentally friendly approach in comparison with other conventional methods. The painless gains from microneedles significantly improves the survival rate of cancer patients. The emergence of versatile and innovative transdermal drug delivery systems presents a prime breakthrough opportunity for safer and more effective therapies, which could meet the demands of cancer diagnosis and treatment through different application scenarios. This review highlights the types of microneedles, fabrication methods and materials, along with the recent advances and opportunities. In addition, this review also addresses the challenges and limitations of microneedles in cancer therapy with solutions through current studies and future works to facilitate the clinical translation of microneedles in cancer therapies.

Dual Effect of Chemo-PDT with Tumor Targeting Nanoparticles Containing iRGD Peptide

Nanotechnology, including self-aggregated nanoparticles, has shown high effectiveness in the treatment of solid tumors. To overcome the limitations of conventional cancer therapies and promote therapeutic efficacy, a combination of PDT and chemotherapy can be considered an effective strategy for cancer treatment. This study presents the development of tumor-targeting polysialic acid (PSA) nanoparticles for chemo-PDT to increase the cellular uptake and cytotoxic effect in cancer cells. Chlorin e6 (Ce6), a photosensitizer, and the iRGD peptide (sequence; cCRGDKGPDC) were conjugated to the amine of N-deacetylated PSA. They generate reactive oxygen species (ROS), especially singlet oxygen (1O2), and target integrin αvβ3 on the cancer cell surface. To offer a chemotherapeutic effect, doxorubicin (Dox) was assembled into the core of hydrophobically modified PSA by connecting it with Ce6; this was followed by its sustained release from the nanoparticles. These nanoparticles are able to generate ROS under 633 nm visible-light irradiation, resulting in the strong cytotoxicity of Dox with anticancer effects in HCT116 cells. PSA nanoparticles with the dual effect of chemo-PDT improve conventional PDT, which has a poor ability to deliver photosensitizers to cancer cells. Using their combination with Dox chemotherapy, rapid removal of cancer cells can be expected.

Peptide functionalized nanocarriers for targeted drug delivery in cancer therapy.

The intrinsic limitations of conventional cancer therapies have prompted the development of nanocarriers for more effective and safer cancer treatment. Amongst these, nanocarriers functionalized with tumor-targeting moieties have been utilized to enhance delivery of cancer therapeutics. However, recent reports have revealed that only a modest increase in tumor targeting is typically achieved with this approach. Poor tumor accumulation is largely due to formation of a serum protein corona on the surface of the nanocarriers in circulation, which hinders targeting and leads to nonspecific tissue distribution, immune recognition and rapid blood clearance. Here, we present three highly efficient tumor-targeting nanocarriers that overcome the aforementioned issues. These nanocarriers are functionalized with the acidity-triggered rational membrane (ATRAM) peptide that facilitates internalization specifically into cancer cells within the acidic tumor microenvironment. The first system is a hybrid nanocarrier that consists of a drug-loaded polylactic-co-glycolic acid (PLGA) core covalently ‘wrapped’ with a crosslinked bovine serum albumin (BSA) shell. Second are upconversion mesoporous silica nanospheres (UMSNs), with combined photodynamic therapy, photothermal therapy and imaging capabilities, that consist of a lanthanide-doped core ‘wrapped’ with lipid-polyethylene glycol (DSPE-PEG-maleimide). The final system consists of drug-loaded mesoporous silica nanoparticles (MSNs) coated with a lipid bilayer composed of DPPC/Chol/DSPE-PEG-mal. The lipid coat is then functionalized with programmed death receptor ligand-1 antibody (anti-PD-L1 antibody, atezolizumab) to disrupt the programmed death 1 (PD-1) interaction that inhibits the anticancer activity of tumor-infiltrating immune cells. In all three systems, the BSA or lipid coats serve to minimize interactions with serum proteins, which allows the nanocarriers to evade immune recognition and extends the in vivo circulation half-life. All three systems exhibit remarkable tumor-targeting efficiency leading to highly potent anticancer activity, while exhibiting negligible toxicity to healthy tissue. Thus, all three systems represent highly promising nanoplatforms for the targeted delivery of cancer therapeutics.

Senescent cancer cell vaccines induce cytotoxic T cell responses targeting primary tumors and disseminated tumor cells

BackgroundImmune tolerance contributes to resistance to conventional cancer therapies such as radiation. Radiotherapy induces immunogenic cell death, releasing a burst of tumor antigens, but this appears insufficient to stimulate an...

Modulating Glycolysis to Improve Cancer Therapy.

Cancer cells undergo metabolic reprogramming and switch to a 'glycolysis-dominant' metabolic profile to promote their survival and meet their requirements for energy and macromolecules. This phenomenon, also known as the 'Warburg effect,' provides a survival advantage to the cancer cells and make the tumor environment more pro-cancerous. Additionally, the increased glycolytic dependence also promotes chemo/radio resistance. A similar switch to a glycolytic metabolic profile is also shown by the immune cells in the tumor microenvironment, inducing a competition between the cancer cells and the tumor-infiltrating cells over nutrients. Several recent studies have shown that targeting the enhanced glycolysis in cancer cells is a promising strategy to make them more susceptible to treatment with other conventional treatment modalities, including chemotherapy, radiotherapy, hormonal therapy, immunotherapy, and photodynamic therapy. Although several targeting strategies have been developed and several of them are in different stages of pre-clinical and clinical evaluation, there is still a lack of effective strategies to specifically target cancer cell glycolysis to improve treatment efficacy. Herein, we have reviewed our current understanding of the role of metabolic reprogramming in cancer cells and how targeting this phenomenon could be a potential strategy to improve the efficacy of conventional cancer therapy.

LGBM-ACp: an ensemble model for anticancer peptide prediction and in silico screening with potential drug targets.

Conventional cancer therapies are highly expensive and have serious complications. An alternative approach now emphasizes on the development of small, biologically active peptides without acute toxicity. Experimental screening to find curative anticancer peptides (ACP) often gives rise to multiple obstacles and is time dependent. Consequently, developing an effective computational technique to identify promising ACP candidates prior to preclinical research is in high demand. This study proposed a machine-learning framework that used the light gradient-boosting machine as a classifier and two compositional and two binary profile features as input. The ensemble model displayed an accuracy, MCC, and AUROC of 97.52%, 0.91, and 0.98, respectively, which outclassed most of the existing sequence-based computational tools. A distinct dataset of non-mutagenic, non-toxic, and non-inhibitory Cytochrome P-450 peptides was used to validate the hybrid model. The most relevant ACP in the alternative dataset was compared with two standard ACPs, beta defensin 2, and cecropin-A. Molecular docking of the predicted peptide revealed that it has a strong binding affinity with twenty-five anticancer drug targets, most notably phosphoenolpyruvate carboxykinase (- 7.2kcal/mol). Additionally, molecular dynamics simulation and principal component analysis supported the stability of the peptide-receptor complex. Overall, the present findings will take a step forward in rational drug design through rapid identification and screening of therapeutic peptides.

The Advancement of Biodegradable Polyesters as Delivery Systems for Camptothecin and Its Analogues-A Status Report.

Camptothecin (CPT) has demonstrated antitumor activity in lung, ovarian, breast, pancreas, and stomach cancers. However, this drug, like many other potent anticancer agents, is extremely water-insoluble. Furthermore, pharmacology studies have revealed that prolonged schedules must be administered continuously. For these reasons, several of its water-soluble analogues, prodrugs, and macromolecular conjugates have been synthesized, and various formulation approaches have been investigated. Biodegradable polyesters have gained popularity in cancer treatment in recent years. A number of biodegradable polymeric drug delivery systems (DDSs), designed for localized and systemic administration of therapeutic agents, as well as tumor-targeting macromolecules, have entered clinical trials, demonstrating the importance of biodegradable polyesters in cancer therapy. Biodegradable polyester-based DDSs have the potential to deliver the payload to the target while also increasing drug availability at intended site. The systemic toxicity and serious side-effects associated with conventional cancer therapies can be significantly reduced with targeted polymeric systems. This review elaborates on the use of biodegradable polyesters in the delivery of CPT and its analogues. The design of various DDSs based on biodegradable polyesters has been described, with the drug either adsorbed on the polymer's surface or encapsulated within its macrostructure, as well as those in which a hydrolyzed chemical bond is formed between the active substance and the polymer chain. The data related to the type of DDSs, the kind of linkage, and the details of in vitro and in vivo studies are included.

Oncolytic Virotherapy.

Oncolytic virotherapy opens up avenues for cancer treatment by selectively targeting the cancer cells and destructs them either through direct lysis or by inducing an immune response in the tumor microenvironment. This platform technology utilizes a diverse range naturally existing or genetically modified oncolytic viruses for their immunotherapeutic potential. Due to the limitations associated with the conventional cancer therapies, immunotherapies using oncolytic viruses (OVs) have generated a great deal of interest in the modern era. Currently, several oncolytic viruses have entered clinical trials and have proven successful for a number of different cancers as monotherapies as well as in combination with the standard treatment methods like chemotherapy, radiotherapy, or immunotherapy. Efficacy of OVs can be further enhanced by utilizing several approaches. Efforts of the scientific community for getting better knowledge of individual patient tumor immune responses will enable medical community to treat cancer patients more precisely. In this regard, OV seems to be a part of multimodality cancer treatment option in the near future. In this chapter, the fundamental characteristics and mechanism of actions of oncolytic viruses are initially described and then overview of the important clinical trials of various oncolytic viruses for a number of cancers is presented.

Photoresponsive Inorganic Nanomaterials in Oncology.

The diagnosis and treatment of cancer are continuously evolving in search of more efficient, safe, and personalized approaches. Therapies based on nanoparticles or physical stimuli-responsive substances have shown great potential to overcome the inherent shortcomings of conventional cancer therapies. In fact, nanoparticles may increase the half-life of chemotherapeutic agents or promote the targeting in cancer tissues while physical stimuli-responsive substances are more effective and safer with respect to traditional chemotherapeutic agents because of the possibility to be switched on only when needed. These 2 approaches can be combined by exploiting the ability of some inorganic nanomaterials to be activated by light, ultrasounds, magnetic fields, or ionizing radiations. Albeit the development of stimuli-responsive materials is still at the early stages, research in this field is rapidly growing since they have important advantages with respect to organic nanoparticles or molecular substances, like higher stability, and higher efficiency in converting the stimulus in heat or, in some cases, reactive oxygen species. On the other hand, the translation process is slowed down by issues related to safety and quality of the formulations. This literature review summarizes the current advancements in this research field, analysing the most promising materials and applications.

In silico Identification of Hypoxic Signature followed by reverse transcription-quantitative PCR Validation in Cancer Cell Lines

Hypoxic tumor microenvironment is one of the important impediments for conventional cancer therapy. This study aimed to computationally identify hypoxia-related messenger RNA (mRNA) signatures in nine hypoxic-conditioned cancer cell lines and investigate their role during hypoxia. Nine RNA sequencing (RNA-Seq) expression data sets were retrieved from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified in each cancer cell line. Then 23 common DEGs were selected by comparing the gene lists across the nine cancer cell lines. Reverse transcription-quantitative PCR (qRT-PCR) was performed to validate the identified DEGs. By comparing the data sets, GAPDH, LRP1, ALDOA, EFEMP2, PLOD2, CA9, EGLN3, HK, PDK1, KDM3A, UBC, and P4HA1 were identified as hub genes. In addition, miR-335-5p, miR-122-5p, miR-6807-5p, miR-1915-3p, miR-6764-5p, miR-92-3p, miR-23b-3p, miR-615-3p, miR-124-3p, miR-484, and miR-455-3p were determined as common micro RNAs. Four DEGs were selected for mRNA expression validation in cancer cells under normoxic and hypoxic conditions with qRT-PCR. The results also showed that the expression levels determined by qRT-PCR were consistent with RNA-Seq data. The identified protein-protein interaction network of common DEGs could serve as potential hypoxia biomarkers and might be helpful for improving therapeutic strategies.

Mechanism Research and Application for Ginsenosides in the Treatment of Hepatocellular Carcinoma.

Ginsenosides, the main active pharmacological ingredients of ginseng, have been widely used for the treatment of numerous carcinomas. Hepatocellular carcinoma (HCC) is 3rd leading malignant tumor in terms of mortality worldwide. Accumulating evidence indicates that ginsenosides play a vital role in the prevention and treatment of HCC. Ginsenosides can significantly improve the symptoms of HCC, and their anticancer activity is mainly involved in inhibiting proliferation and migration, inducing cell cycle arrest at the G0/G1 phase, promoting caspase-3 and 8-mediated apoptosis, regulating autophagy related to Atg5, Atg7, Atg12, LC3-II, and PI3K/Akt pathways, and lowering invasion and metastasis associated with decreased nuclear translocation of NF-κB p65 and MMP-2/9, increasing IL-2 and IFN-γ levels to enhance immune function, as well as regulating the gut-liver axis. In addition, ginsenosides can be used as an adjuvant to conventional cancer therapies, enhancing sensitivity to chemotherapy drugs, and improving efficacy and/or reducing adverse reactions through synergistic effects. Therefore, the current manuscript discusses the mechanism and application of ginsenosides in HCC. It is hoped to provide theoretical basis for the treatment of HCC with ginsenosides.

AIEgens for synergistic anticancer therapy.

Cancer is a mortal disease that can invade other parts of the body and cause severe complications. Despite their continuous progress, conventional cancer therapies including surgery, chemotherapy, and radiation therapy have their inherent limitations. To improve the precision of cancer treatment, maximize the therapeutic effect and minimize mortality, synergistic therapies combining imaging guiding technologies, phototherapy, and other therapies have emerged due to the mutually strengthening therapeutic efficacy. However, traditional organic phototherapeutic agents are limited since their aggregation in aqueous media usually affects both their luminescence behavior and therapeutic effect. In contrast, aggregate-induced emission luminogens (AIEgens) provide an ideal solution to develop phototherapy with bright fluorescence and a significant treatment effect in the aggregate state. Combining AIE-based phototherapy and conventional therapies benefits from synergistic effects and extends the potential of developing accurate cancer therapy. AIE-based synergistic therapy has been popularly discussed with such unexplored potential in recent years. This review will introduce the most recent progress of AIE-based synergistic cancer therapy.

Precision medicine: Ray of hope in overcoming cancer multidrug resistance.

Multi-drug resistance (MDR) developed in response to chemotherapy is one of the prominent causes of therapeutic failure. The major underlying factors that contribute to such malignancies include tumor microenvironment, genetic alterations, changes at the cellular level and most of all the heterogeneity of tumors. Recent advances in the field of oncology have prompted a mechanistic understanding of the human genome which is responsible for such alterations, upon which the therapy would be designed. Such an approach that administers drugs by targeting the molecular changes is attributed to precision medicine. Precision medicine helps design therapy as per the requirement of patients based on the sharing of similar complex tumor environments. This revolutionized approach would help in early detection, better targeting, improved patient compliance and survival along with much reduced toxicity otherwise evidenced in conventional cancer therapy. This review discusses the cause of MDR, highlighting the role of precision medicine in overcoming such critical events. Major limitations and future prospects are also highlighted.

Nobiletin is capable of regulating certain anti-cancer pathways in a colon cancer cell line.

Natural remedies have the potential to improve conventional cancer therapies and enhance patient outcomes. Citrus polymethoxyflavone nobiletin has been demonstrated to have anticancer effects on several cancer cell lines. In this study, the anti-cancer activity of nobiletin is investigated on Bax, Bcl-2, HO-1, VEGF, MMP-7, Akt, p70S6K, 4EBP1, tuberin, and hamartin. IC50 doses were 403.6µM, 264µM, and 40µM, respectively, at 24, 48, and 72h. Akt, Bax, Bcl-2, and p70S6K levels decreased at nobiletin concentrations greater than 100, 250, 500, and 1000µM, respectively. Nobiletin decreased HO-1 and VEGF levels at concentrations greater than 100µM. MMP-7 levels interestingly increased at 100µM but decreased at doses greater than 250µM. 4EBP1 levels increased, except from 2000 and 3000µM nobiletin concentrations. Tuberin levels increased at 10, 50, and 3000µM, decreased at 250µM, and remained unchanged at the rest of the concentrations. Nobiletin decreased hamartin levels; however, this decrease was statistically significant only at 10, 100, 250, 500, and 3000µM concentrations. Decreased Akt activity might be interpreted as nobiletin inhibiting mTORC1 activity and subsequently increased 4EBP1 and unchanged or decreased p70S6K protein levels. Akt activity can cause suppression of angiogenesis via decreased VEGF, MMP-7, and HO-1 levels at concentrations greater than 500µM. These results are significant as a nobiletin therapy could prevent colon cancer progression by inhibiting Akt signaling and angiogenesis.

Canvassing Prospects of Glyco-Nanovaccines for Developing Cross-Presentation Mediated Anti-Tumor Immunotherapy.

In view of the severe downsides of conventional cancer therapies, the quest of developing alternative strategies still remains of critical importance. In this regard, antigen cross-presentation, usually employed by dendritic cells (DCs), has been recognized as a potential solution to overcome the present impasse in anti-cancer therapeutic strategies. It has been established that an elevated cytotoxic T lymphocyte (CTL) response against cancer cells can be achieved by targeting receptors expressed on DCs with specific ligands. Glycans are known to serve as ligands for C-type lectin receptors (CLRs) expressed on DCs, and are also known to act as a tumor-associated antigen (TAA), and, thus, can be harnessed as a potential immunotherapeutic target. In this scenario, integrating the knowledge of cross-presentation and glycan-conjugated nanovaccines can help us to develop so called 'glyco-nanovaccines' (GNVs) for targeting DCs. Here, we briefly review and analyze the potential of GNVs as the next-generation anti-tumor immunotherapy. We have compared different antigen-presenting cells (APCs) for their ability to cross-present antigens and described the potential nanocarriers for tumor antigen cross-presentation. Further, we discuss the role of glycans in targeting of DCs, the immune response due to pathogens, and imitative approaches, along with parameters, strategies, and challenges involved in cross-presentation-based GNVs for cancer immunotherapy. It is known that the effectiveness of GNVs in eradicating tumors by inducing strong CTL response in the tumor microenvironment (TME) has been largely hindered by tumor glycosylation and the expression of different lectin receptors (such as galectins) by cancer cells. Tumor glycan signatures can be sensed by a variety of lectins expressed on immune cells and mediate the immune suppression which, in turn, facilitates immune evasion. Therefore, a sound understanding of the glycan language of cancer cells, and glycan-lectin interaction between the cancer cells and immune cells, would help in strategically designing the next-generation GNVs for anti-tumor immunotherapy.

Supramolecular Loading of DNA Hydrogels with Dye-Drug Conjugates for Real-Time Photoacoustic Monitoring of Chemotherapy.

A longstanding problem with conventional cancer therapy is the nonspecific distribution of chemotherapeutics. Monitoring drug release in vivo via noninvasive bioimaging can thus have value, but it is difficult to distinguish loaded from released drug in live tissue. Here, this work describes an injectable supramolecular hydrogel that allows slow and trackable release of doxorubicin (Dox) via photoacoustic (PA) tomography. Doxis covalently linked with photoacoustic methylene blue (MB) to monitor Doxbefore, during, and after release from the hydrogel carrier. The conjugate (MB-Dox) possesses an IC50 of 161.4× 10-9 m against human ovarian carcinoma (SKOV3) cells and loads into a DNA-clad hydrogel with 91.3% loading efficiency due to MB-Dox's inherent intramolecular affinity to DNA. The hydrogel is biodegradable by nuclease digestion, which causes gradual release of MB-Dox. This release rate is tunable based on the wt% of the hydrogel. This hydrogel maintains distinct PA contrast on the order of days when injected in vivo and demonstrates activatable PA spectral shifts during hydrogel degradation. The released and loaded payload can be imaged relative to live tissue via PA and ultrasound signal being overlaid in real-time. The hydrogel slowed the rate of the murine intraperitoneal tumor growth 72.2% more than free Dox.

Recent advances in cold atmospheric plasma (CAP) for breast cancer therapy.

The serious problems of conventional breast cancer therapy strategies such as drug resistance, severe side effects, and lack of selectivity prompted the development of various cold atmospheric plasma (CAP) devices. Due to its advanced technology, CAP can produce a unique environment rich in reactive oxygen and nitrogen species (RONS), photons, charged ions, and an electric field, making it a promising revolutionary platform for cancer therapy. Despite substantial technological successes, CAP-based therapeutic systems are encounter with distinct limitations, including low control of the generated RONS, poor knowledge about its anticancer mechanisms, and challenges concerning designing, manufacturing, clinical translation, and commercialization, which must be resolved. The latest developments in CAP-based therapeutic systems for breast cancer treatment are discussed in this review. More significantly, the integration of CAP-based medicine approaches with other breast cancer therapies, including chemo- and nanotherapy is thoroughly addressed.

Nanomedicine for advanced cancer immunotherapy.

Immunotherapy has emerged as a powerful strategy for liquid tumors to overcome the limitations of conventional cancer therapies. The nanomedical delivery system offers the possibility of enhancing cancer immunotherapy and expanding it to solid tumors. Here, we discuss the applications of medical nanoparticles to improve the efficacy of immunotherapy. We first focus on nanomedical particles used in cancer immunotherapy to deliver peptide and mRNA vaccines to the lymph nodes; and the exosome-based therapeutic cancer vaccine. Next, we highlight the applications of nanomedicine in immune checkpoint therapy to prolong the therapeutic effects, enhance tumor-targeting ability, and overcome drug resistance. We also evaluate the roles of nanomedical particles in oncolytic viral treatment, enabling the systemic injection of viruses or oncolytic plasmids/oncotoxic proteins; and virus entry in a receptor-independency manner. Lastly, we focus on nanoparticles in chimeric antigen receptor (CAR) T cell therapy to engineer CAR T cells, enhancing T cell proliferation and infiltration. We envision the nanomedical particles enhancing the therapeutic effects of immunotherapy and revolutionizing cancer therapy in the foreseeable future.

Targeting telomerase reverse transcriptase with the covalent inhibitor NU-1 confers immunogenic radiation sensitization

Beyond synthesizing telomere repeats, the telomerase reverse transcriptase (TERT) also serves multiple other roles supporting cancer growth. Blocking telomerase to drive telomere erosion appears impractical, but TERT's non-canonical activities have yet to be fully explored as cancer targets. Here, we used an irreversible TERT inhibitor, NU-1, to examine impacts on resistance to conventional cancer therapies. Invitro, inhibiting TERT sensitized cells to chemotherapy and radiation. NU-1 delayed repair of double-strand breaks, resulting in persistent DNA damage signaling and cellular senescence. Although NU-1 alone did not impact growth of syngeneic CT26 tumors in BALB/c mice, it dramatically enhanced the effects of radiation, leading to immune-dependent tumor elimination. Tumors displayed persistent DNA damage, suppressed proliferation, and increased activated immune infiltrate. Our studies confirm TERT's role in limiting genotoxic effects of conventional therapy but also implicate TERT as a determinant of immune evasion and therapy resistance.

Using omics approaches to dissect the therapeutic effects of Chinese herbal medicines on gastrointestinal cancers.

Chinese herbal medicines offer a rich source of anti-cancer drugs. Differences between the pharmacology of Chinese herbal medicines and modern synthetic chemicals hinder the development of drugs derived from herbal products. To address this challenge, novel omics approaches including transcriptomics, proteomics, genomics, metabolomics, and microbiomics have been applied to dissect the pharmacological benefits of Chinese herbal medicines in cancer treatments. Numerous Chinese herbal medicines have shown potential anti-tumor effects on different gastrointestinal (GI) cancers while eliminating the side effects associated with conventional cancer therapies. The present study aimed to provide an overview of recent research focusing on Chinese herbal medicines in GI cancer treatment, based on omics approaches. This review also illustrates the potential utility of omics approaches in herbal-derived drug discovery. Omics approaches can precisely and efficiently reveal the key molecular targets and intracellular interaction networks of Chinese herbal medicines in GI cancer treatment. This study summarizes the application of different omics-based approaches in investigating the effects and mechanisms of Chinese herbal medicines in GI cancers. Future research directions are also proposed for this area of study.