Current Cancer Therapy Reviews - Volume 20, Issue 4, 2024

Colorectal cancer (CRC) is the third most common cancer worldwide, and the incidence of CRC seems to increase gradually. The survival of CRC varies in different countries, attributed to the screening program. Generally, diagnostic approaches for CRC can be divided into visual detection methods and laboratory methods. Colonoscopy, sigmoidoscopy, and computed tomography colonography are considered visual methods widely used in cancer detection. Although visual methods provide some benefits, some disadvantages such as late detection, are present, making them useless in rapidly progressing CRC patients. On the other hand, laboratory tests are developed to compensate for the disadvantages of visual methods. More recent progression in laboratory tests makes them able to superfine detection of CRC. For instance, molecular and genetic methods based on the components of cancer cells, like nucleic acid and proteins, can prognosticate further cancer development in susceptible patients. Alongside new therapeutic approaches developed within decades, the number of CRC detection methods has increased, which aims to reduce the duration between cancer initiation and detection. This review sought to survey the CRC detection methods, including conventional and recently-developed methods, to provide better insight into CRC screening.

Cancer is one of the fatal diseases leading to a high mortality rate. The conventional formulations available for the treatment of cancer are associated with several drawbacks. The major ones are increased side effects due to improper tumor selectivity, metastasis of cancer cells and development of multi-drug resistance to available chemotherapeutic drugs. The development of nanobased formulations for the treatment of cancer has been found to be beneficial up to a great extent. Mesoporous Silica nanoparticles are one of the nanotechnology-based formulations that could overcome major disadvantages associated with conventional therapy, such as metastasis, multi-drug resistance and side effects to normal cells. MSN-based nanoformulations could provide dual therapeutic effects against cancer cells. Due to their small size and large surface, which could be functionalized by using different targeting and therapeutic moieties, they provide targeted and enhanced drug delivery. This review highlights Mesoporous silica nanoparticles along with their properties, drug encapsulation and various applications in drug delivery, such as multi-targeting strategy, and multimodal combined therapy by using ultrasound, photodynamic etc. In the future, MSN-based nanomedicines could be used to develop other innovative strategies for cancer treatment.

Photosensitizers (PS) are effective in treating a wide range of tumours using the timetested technique of photodynamic therapy (PDT). Light has been employed for centuries as a curative modality due to its efficacy. Since the effects of using certain dyes in conjunction with light irradiation were first proven around the turn of the 20th century, new PDT methods have been created. Current research focuses mostly on methods to lessen or eliminate unwanted side effects and enhance the drug's pharmacokinetic qualities. The FDA's decision to approve PDT as the first drug/device combo is not surprising, given the widespread curiosity and volume of published material on the subject. In PDT, light energy is combined with a PS to destroy tumour cells after its activation by light. In comparison to chemotherapy and/or radiation treatment, PDT often has fewer adverse effects and is safer. Several different PSs may be used to diagnose tumours, in addition to their therapeutic use. Photodynamic diagnostics (PDD) is the term used to describe methods like these. In this review, we present a high-level introduction to the diagnostic and therapeutic uses of PDT in cancer. The need of developing predictors to determine the response to therapy will be explored in relation to the assessment of PDT therapeutic effectiveness in the clinic. The use of PDT to treat different tumours will also be shown through case studies. The potential of combining PDT with other forms of treatment, such as chemotherapy, radiation, surgery, and immunotherapy, to increase efficacy against tumours will also be highlighted. Results from PDT alone may not be as good as those from PDT combined with other therapies. It's also possible that lower dosages used in combination therapy will have fewer adverse effects and provide better outcomes than each individual treatment would. It is possible that the therapeutic uses of PDT might be broadened by a greater knowledge of the efficacy of PDT in a combination context in the clinic, as well as the optimisation of such complicated multimodal therapies.

Chemotherapy is the mainstay of therapeutic cancer therapy; however, the development of resistance typically makes it less effective. There are continuous efforts by researchers to find novel lead compounds with potent anti-cancer activity. Generally, synthetic or natural heterocyclic compounds have been investigated in detail as a scaffold for cancer therapeutics. Among them, indole, owing to its unique physiochemical and biological properties, provides a promising platform for the development of pharmacophores for drug development against cancer, acting via various mechanisms. Till now, several indole-based derivatives have been identified as anti-cancer agents, which are either being used in clinics or are in various phases of clinical trials, suggesting their importance in anti-cancer drug development. These anti-cancer drugs have been classified into different classes depending on their mechanism of action. For example, histone deacetylase inhibitors (HDAC inhibitors), silent mating type information regulation 2 homolog (SIRT) inhibitors, tubulin inhibitors, proviral insertion site in Moloney murine leukemia virus (Pim) inhibitors, DNA Topoisomerase inhibitors, and kinase inhibitors. In this review, the author's approach is to compile the recent developments on indole-based anti-cancer drugs and provide insight into the respective structureactivity relationships (SARs) of the compounds. We hope the review will provide a thorough understanding to the reader and guide to developing novel and potent indole-based anticancer agents against drug-sensitive and drug-resistant cancer in the future.

Cancer is one of the biggest threats to human health with a global incidence of 23.6 million, mortality of 10 million, and an estimated 250 million lost in disability-adjusted life years (DALYs) each year. Moreover, the incidence, mortality, and DALYs have increased over the past decade by 26.3%, 20.9%, and 16.0%, respectively. Despite significant evolutions in medical therapy and advances in the DNA microarray, proteomics technology, and targeted therapies, anticancer drug resistance continues to be a growing concern and invites regular discovery of potent agents. One such agent is the microbe-producing bioactive compounds like Streptomyces, which are proving increasingly resourceful in anticancer therapy of the future. Streptomyces, especially the species living in extreme conditions, produce bioactive compounds with cytolytic and anti-oxidative activity which can be utilized for producing anticancer and chemo-preventive agents. The efficacy of the derived compounds has been proven on cell lines and some of these have already established clinical results. These compounds can potentially be utilized in the treatment of a variety of cancers including but not limited to colon, lung, breast, GI tract, cervix, and skin cancer. The Streptomyces, thus possess the armory to fuel the anticancer agents of the future and help address the problem of rising resistance to currently available anti-cancer drugs. We conducted a state-of-art review using electronic databases of PubMed, Scopus, and Google scholar with an objective to appraise the currently available literature on Streptomyces as a source of anti-cancer agents and to compile the clinically significant literature to update the clinicians.

Background: Colorectal cancer (CRC) is one of the most prevalent cancers worldwide. Objective: Considering the side effects of chemotherapy treatments, we reviewed the anti-cancer effects and mechanisms of bromelain on colon cancer cells in this study. Methods: The PRISMA guidelines were followed in the design of this systematic review. Various databases, including PubMed, Web of Science, Cochrane Library, and Scopus, were thoroughly searched. Finally, 14 articles were retrieved after considering the study's inclusion and exclusion criteria. The desired data were extracted, entered into an Excel file, and the study results were reviewed. Results: According to the included studies, bromelain can significantly reduce the survival and death of cloned cancer cells through different mechanisms. These mechanisms include impeding tumor growth and metastasis by reducing mucins production/secretion and increasing/reducing reactive oxygen species (ROS) production. Moreover, bromelain induces apoptosis via reduced expression of Bcl-2, extracellular signal-related kinase (ERK), Akt, activation caspase system (caspase-3, 7, 8, and 9), and extranuclear p53. Ferroptosis was another mechanism of causing cell death. In addition, bromelain activates the autophagy pathway, lysosome formation, and deregulation of other autophagyrelated proteins. Conclusion: Bromelain effectively inhibits colon cancer cells' growth, proliferation, and metastasis and reduces their survival by different mechanisms. Therefore, after examining clinical studies, it can be used as an effective drug for treating CRC.

Significance of the Study: In silico analysis is frequently used in physicochemical characterisation, the discovery and improvement of novel compounds with affinity to a target, and the elucidation of absorption, distribution, metabolism, excretion, and toxicity features. Aim and Objective: The aim of this study is to assess the efficacy of Nigella sativa and Cuscuta reflexa in targeting Bcl2-antiapoptotic protein in Oral Squamous Cell Carcinoma through in silico analysis. Materials and Methods: The present study was designed to formulate a drug against Oral Squamous cell carcinoma against the target protein Bcl-2. Protein Database (PDB) was used to select and analyse the protein. Based on the literature search, the original molecules selected were thymoquinone, tannin pyrogallol, Cuscutin, kaempferol, nigellicine and the ligand structures were obtained ZINC15 database. Target protein structure was recognised through Protein sequence from PB (Protein Data Bank). Swiss ADME was used for assessing the properties of the molecules. Twenty new molecules were identified from zinc pharmer and docking was done for all the 20 using Swiss dock. Binding energy was assessed and compared with the original molecules. Results: ZINC73690300 and ZINC73690304 had better binding energy than that of the original molecules. Both molecules can be potential candidates for Bcl-2 inhibition to prevent OSCC. Conclusion: The present study evaluated the binding energy and bioavailability of the combined extract, thus attempting to predict the target ligand binding between the compounds in OSCC before attempting in vitro studies.

Background: Several investigations have demonstrated that vitamins can treat or prevent cancer by altering actin filaments and inhibiting cell migration and proliferation. Vitamins D and E are fat-soluble. This research aims to determine the short-term impact of vitamin D and E on the mechanical properties of breast cancer cells before comparing them with normal breast cells. Methods: Atomic force microscopy (AFM) was used to examine the deformation of MCF-10 normal breast cells, MCF-7 breast cancer cells, and MCF-7 breast cancer cells treated with 0.03 μM vitamin D and 16 μM vitamin E solutions. Young's modulus was calculated employing the Hertz model to determine cell stiffness. Results: The Young's modulus of vitamin D-treated cancer cells (585.8 Pa) was substantially similar to that of normal cells (455.6 Pa). Nevertheless, vitamin E treatment did not affect Young's modulus of cancer cells, which remained remarkably similar to that of untreated cancer cells (216.6 and 203.4 Pa, respectively). Conclusion: Unlike vitamin E, vitamin D enhances the stiffness of tumor cells and makes their mechanical properties similar to normal cells by interfering with actin filaments and cell skeletons, which may inhibit tumor cell migration. Based on these findings, vitamin D appears to be an effective drug for cancer treatment.