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Special Issue "Advances in Anticancer Drugs and Pharmacotherapy of Cancer"

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Drug Development".

Deadline for manuscript submissions: 15 October 2023 | Viewed by 13733

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Special Issue Editors

Dr. Long Chiau Ming

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Guest Editor

School of Medical and Life Sciences, Sunway University, Sunway City, Malaysia
Interests: clinical medicine; pharmacy; clinical pharmacology; patient safety; natural products
Special Issues, Collections and Topics in MDPI journals

Dr. Muhammad Abdul Hadi

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Guest Editor

College of Pharmacy, QU Health, Qatar University, Doha, Qatar
Interests: mixed-methods; health services research; medication safety; adherence
Special Issues, Collections and Topics in MDPI journals

Dr. Md. Sanower Hossain

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Guest Editor

Centre for Sustainability of Ecosystem and Earth Resources (Pusat ALAM), Universiti Malaysia Pahang, Kuantan 26300, Pahang, Malaysia
Interests: pharmaceutical technology; drug safety and efficacy; drug delivery; antibiotic resistance; infectious diseases; cancer biology; medicinal plants

Dr. Bey-Hing Goh

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Guest Editor

School of Pharmacy, Monash University Malaysia, Subang Jaya, Malaysia
Interests: natural products; microbial drug discovery; molecular oncology; ethnopharmacology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The pharmacotherapy of cancer has experienced some encouraging novel developments. A new armamentarium of anticancer drugs and their delivery have led to improvements not only in efficacy and safety profiles but also the quality of life both pre and post treatment.

The regulatory approval of several new targeted immunotherapies indicates their success in clinical trials for treating multiple types of cancer. Using a targeted immunotherapy approach, oncologists can firstly screen for protein or genetic abnormalities in a patient’s tumor and then match those with appropriate immunotherapies. Immunotherapy boosts the body’s immune system to attack cancer cells through applications of CAR T-cell therapy, immune checkpoint inhibitors, monoclonal antibodies, treatment vaccines, and immune system modulators.

In terms of drug delivery systems, the use of innovative chemotherapy delivery systems, such as pressurized intraperitoneal aerosol chemotherapy (PIPAC), has significantly reduced the severity of the side effects of systematically delivered chemotherapy. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel technique delivering normothermic chemotherapy into the abdominal cavity as an aerosol under pressure. Early stage trials involved administering intraperitoneal chemotherapy to multiple areas of metastasis in the abdominal area. The involved tumors normally consist of small nodules that have proliferated to such a widespread extent that they are challenging to treat using surgical incision. Likewise, conventional intravenous chemotherapy is inferior when compared with PIPAC, which applies the same standard technique used in diagnostic laparoscopy. Such direct delivery of anticancer drugs into the abdomen via a nebulizer pen, channeling an aerosolized form of chemotherapy deep into the abdominal crevices, ensures that residual drugs are subsequently removed.

This Special Issue of Cancers will cover theoretical and applied aspects of cancer drug discovery, formulation, product development, and clinical practices. Submissions presenting research related to chemical identification, in vitro/in vivo/in silico evaluation of anticancer agents, including natural products, or complementary medicine in original research and review articles are welcome.

Dr. Long Chiau Ming
Dr. Muhammad Abdul Hadi
Dr. Md. Sanower Hossain
Dr. Bey-Hing Goh
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

anticancer drugs
hormone therapy
immunotherapy
complementary medicine
dosage form design
chemotherapy

Published Papers (13 papers)

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Research

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Open AccessArticle

Discovery of Novel Bioactive Tanshinones and Carnosol Analogues against Breast Cancer

Miguel A. González-Cardenete

Natalia González-Zapata

Lucinda Boyd

and

Fatima Rivas

Cancers 2023, 15(4), 1318; https://doi.org/10.3390/cancers15041318 - 19 Feb 2023

Viewed by 623

Abstract

The abietane diterpenoids ferruginol (1), tanshinone IIA (3), and carnosol (4) are well-known for their interesting pharmacological properties, including antitumor, similar to other natural and semisynthetic abietanes. In this study, a pair of semisynthetic C18-functionalized analogues of 3 and 4 were prepared from the commercially available (+)-dehydroabietylamine or readily obtained methyl dehydroabietate. Semisynthetic ferruginol (1) and some selected analogues, together with the synthesized analogues, were tested in vitro for the inhibition of proliferation in four breast cancer cell lines, SUM149, MDA-MB231, T47D, and MCF07. As a result, several tested abietane analogues decreased cell proliferation and enhanced cell death, with IC₅₀ in the range 1.3–18.7 μM. This work demonstrates the antitumor activities of two tested compounds, making these molecules interesting for the development of new anticancer agents. Full article

(This article belongs to the Special Issue Advances in Anticancer Drugs and Pharmacotherapy of Cancer)

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Open AccessArticle

Toxicity of Asciminib in Real Clinical Practice: Analysis of Side Effects and Cross-Toxicity with Tyrosine Kinase Inhibitors

Magdalena Sierra Pacho

Juan Antonio Vera Goñi

Melania Moreno Vega

Alberto Alvarez-Larrán

Montse Cortés

Manuel Pérez Encinas

Patricia Carrascosa Mastell

Lucía Villalón Blanco

Juan Manuel Alonso-Domínguez

María Magdalena Anguita Arance

Araceli Salamanca Cuenca

Antonio Jiménez-Velasco

Santiago Osorio Prendes

Marta Santaliestra

María José Lis Chulvi

Juan Carlos Hernández-Boluda

and

Valentín García-Gutiérrez

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Cancers 2023, 15(4), 1045; https://doi.org/10.3390/cancers15041045 - 07 Feb 2023

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Abstract

(1) Background: Despite the prognostic improvements achieved with tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML), a minority of patients still fail TKIs. The recent introduction of asciminib may be a promising option in intolerant patients, as it is a first-in-class inhibitor with a more selective mechanism of action different from the ATP-competitive inhibition that occurs with TKIs. Therefore, our goal was to analyze toxicities shown with asciminib as well as to study cross-toxicity with previous TKIs. (2) Methods: An observational, multicenter, retrospective study was performed with data from 77 patients with CML with therapeutic failure to second-generation TKIs who received asciminib through a managed-access program (MAP) (3) Results: With a median follow-up of 13.7 months, 22 patients (28.5%) discontinued treatment: 32% (7/22) due to intolerance and 45% (10/22) due to resistance. Fifty-five percent of the patients reported adverse effects (AEs) with asciminib and eighteen percent grade 3–4. Most frequent AEs were: fatigue (18%), thrombocytopenia (17%), anemia (12%), and arthralgias (12%). None of the patients experienced cardiovascular events or occlusive arterial disease. Further, 26%, 25%, and 9% of patients required dose adjustment, temporary suspension, or definitive discontinuation of treatment, respectively. Toxicities under asciminib seemed lower than with prior TKIs for anemia, cardiovascular events, pleural/pericardial effusion, diarrhea, and edema. Cross-toxicity risk was statistically significant for thrombocytopenia, anemia, neutropenia, fatigue, vomiting, and pancreatitis. (4) Conclusion: Asciminib is a molecule with a good safety profile and with a low rate of AEs. However, despite its new mechanism of action, asciminib presents a risk of cross-toxicity with classical TKIs for some AEs. Full article

(This article belongs to the Special Issue Advances in Anticancer Drugs and Pharmacotherapy of Cancer)

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Open AccessArticle

Inhibition of Macropinocytosis Enhances the Sensitivity of Osteosarcoma Cells to Benzethonium Chloride

and

Cancers 2023, 15(3), 961; https://doi.org/10.3390/cancers15030961 - 02 Feb 2023

Viewed by 532

Abstract

Osteosarcoma (OS) is a primary malignant tumor of bone. Chemotherapy is one of the crucial approaches to prevent its metastasis and improve prognosis. Despite continuous improvements in the clinical treatment of OS, tumor resistance and metastasis remain dominant clinical challenges. Macropinocytosis, a form of non-selective nutrient endocytosis, has received increasing attention as a novel target for cancer therapy, yet its role in OS cells remains obscure. Benzethonium chloride (BZN) is an FDA-approved antiseptic and bactericide with broad-spectrum anticancer effects. Here, we described that BZN suppressed the proliferation, migration, and invasion of OS cells in vitro and in vivo, but simultaneously promoted the massive accumulation of cytoplasmic vacuoles as well. Mechanistically, BZN repressed the ERK1/2 signaling pathway, and the ERK1/2 activator partially neutralized the inhibitory effect of BZN on OS cells. Subsequently, we demonstrated that vacuoles originated from macropinocytosis and indicated that OS cells might employ macropinocytosis as a compensatory survival mechanism in response to BZN. Remarkably, macropinocytosis inhibitors enhanced the anti-OS effect of BZN in vitro and in vivo. In conclusion, our results suggest that BZN may inhibit OS cells by repressing the ERK1/2 signaling pathway and propose a potential strategy to enhance the BZN-induced inhibitory effect by suppressing macropinocytosis. Full article

(This article belongs to the Special Issue Advances in Anticancer Drugs and Pharmacotherapy of Cancer)

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Open AccessArticle

Multi-Fold Computational Analysis to Discover Novel Putative Inhibitors of Isethionate Sulfite-Lyase (Isla) from Bilophila wadsworthia: Combating Colorectal Cancer and Inflammatory Bowel Diseases

Muhammad Waqas

Sobia Ahsan Halim

Atta Ullah

Assim Alaa Mohammed Ali

and

Cancers 2023, 15(3), 901; https://doi.org/10.3390/cancers15030901 - 31 Jan 2023

Viewed by 684

Abstract

A glycal radical enzyme called isethionate sulfite-lyase (Isla) breaks the C–S bond in isethionate to produce acetaldehyde and sulfite. This enzyme was found in the Gram-negative, colonial Bilophila wadsworthia bacteria. Sulfur dioxide, acetate, and ammonia are produced by the anaerobic respiration route from (sulfonate isethionate). Strong genotoxic H₂S damages the colon’s mucous lining, which aids in the development of colorectal cancer. H₂S production also contributes to inflammatory bowel diseases such as colitis. Here, we describe the structure-based drug designing for the Isla using an in-house database of naturally isolated compounds and synthetic derivatives. In structure-based drug discovery, a combination of methods was used, including molecular docking, pharmacokinetics properties evaluation, binding free energy calculations by the molecular mechanics/generalized born surface area (MM/GBSA) method, and protein structure dynamics exploration via molecular dynamic simulations, to retrieve novel and putative inhibitors for the Isla protein. Based on the docking score, six compounds show significant binding interaction with the Isla active site crucial residues and exhibit drug-like features, good absorption, distribution, metabolism, and excretion profile with no toxicity. The binding free energy reveals that these compounds have a strong affinity with the Isla. In addition, the molecular dynamics simulations reveal that these compounds substantially affect the protein structure dynamics. As per our knowledge, this study is the first attempt to discover Isla potential inhibitors. The compounds proposed in the study using a multi-fold computational technique may be verified in vitro as possible inhibitors of Isla and possess the potential for the future development of new medications that target Isla. Full article

(This article belongs to the Special Issue Advances in Anticancer Drugs and Pharmacotherapy of Cancer)

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Open AccessArticle

Naturally Isolated Sesquiterpene Lactone and Hydroxyanthraquinone Induce Apoptosis in Oral Squamous Cell Carcinoma Cell Line

and

Cancers 2023, 15(2), 557; https://doi.org/10.3390/cancers15020557 - 16 Jan 2023

Cited by 1 | Viewed by 1088

Abstract

Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers worldwide, especially in Asian countries. The emergence of its drug resistance and its side effects demands alternatives, to improve prognosis. Since the majority of cancer drugs are derived from natural sources, it provides a window to look for more biocompatible alternatives. In this study, two natural compounds, costunolide (CE) and aloe emodin (AE), were isolated from the stem of Lycium shawii. The compounds were examined for their anticancer and apoptotic potentials against OSCC (CAL 27) cells, using an in vitro analysis, such as a MTT assay, scratch assay, gene, and protein expressions. Both compounds, CE and AE, were found to be cytotoxic against the cancer cells with an IC₅₀ value of 32 and 38 µM, respectively. Moreover, the compounds were found to be non-toxic against normal NIH-3T3 cells and comparable with the standard drug i.e., 5-fluorouracil (IC₅₀ = 97.76 µM). These compounds were active against normal cells at higher concentrations. Nuclear staining displayed the presence of apoptosis-associated morphological changes, i.e., karyopyknosis and karyorrhexis in the treated cancer cells. Flow cytometry results further confirmed that these compounds induce apoptosis rather than necrosis, as the majority of the cells were found in the late apoptotic phase. Gene and protein expression analyses showed an increased expression of apoptotic genes, i.e., BAK, caspase 3, 6, and 9. Moreover, the compounds significantly downregulated the expression of the anti-apoptotic (BCL-2 L1), metastatic (MMP-2), and pro-inflammatory (COX-2) genes. Both compounds have shown promising anticancer, apoptotic, and anti-migratory activities against the OSCC cell line (i.e., CAL-27). However, further in vivo studies are required to explore these compounds as anticancer agents. Full article

(This article belongs to the Special Issue Advances in Anticancer Drugs and Pharmacotherapy of Cancer)

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Open AccessArticle

Phytochemical Compounds and Anticancer Activity of Cladanthus mixtus Extracts from Northern Morocco

María Emilia Candela Castillo

Alain Badoc

Ahmed Lamarti

Joaquim C. G. Esteves da Silva

and

Marino B. Arnao

Cancers 2023, 15(1), 152; https://doi.org/10.3390/cancers15010152 - 27 Dec 2022

Viewed by 991

Abstract

Many of the chemotherapeutic drugs for the treatment of cancer are molecules identified and isolated from plants or their synthetic derivatives. This work aimed to identify the bioactive compounds using LC-MS and GC-MS and to evaluate the anticancer activity of the methanolic extracts of roots, stems, leaves, and flowers from Cladanthus mixtus. The anticancer activity was evaluated in vitro against two cancer cell lines: human breast carcinoma (MCF-7) and human prostate carcinoma (PC-3), using the MTT assay and microscopic observation. A human normal lung fibroblast (MRC-5) was included to determine the extract’s safety for non-tumoral cells. The chemical composition results by LC-MS analysis revealed the presence of 24 phenolic compounds. Furthermore, GC-MS analysis allowed the identification of many biomolecules belonging to terpenoids, esters, alcohols, alkanes, fatty acids, organic acids, benzenes, phenols, ketones, carbonyls, amines, sterols, and other groups. The findings suggest that the majority of C. mixtus extracts have antiproliferative activity against two cancer cell lines, MCF-7 and PC-3, and one non-tumoral cell line, MRC-5. The activity was dose-dependent, and the highest effect was obtained with leaf extract in the two cancer cell lines. Moreover, these extracts demonstrated an acceptable toxicological profile against normal cells. Overall, C. mixtus extracts revealed promising antitumor properties provided by their phytochemical composition. Full article

(This article belongs to the Special Issue Advances in Anticancer Drugs and Pharmacotherapy of Cancer)

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Open AccessArticle

Targets, Mechanisms and Cytotoxicity of Half-Sandwich Ir(III) Complexes Are Modulated by Structural Modifications on the Benzazole Ancillary Ligand

M. Isabel Acuña

Ana R. Rubio

Marta Martínez-Alonso

Natalia Busto

Ana María Rodríguez

Nerea Davila-Ferreira

and

Cancers 2023, 15(1), 107; https://doi.org/10.3390/cancers15010107 - 24 Dec 2022

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Abstract

Cancers are driven by multiple genetic mutations but evolve to evade treatments targeting specific mutations. Nonetheless, cancers cannot evade a treatment that targets mitochondria, which are essential for tumor progression. Iridium complexes have shown anticancer properties, but they lack specificity for their intracellular targets, leading to undesirable side effects. Herein we present a systematic study on structure-activity relationships of eight arylbenzazole-based Iridium(III) complexes of type [IrCl(Cp*)], that have revealed the role of each atom of the ancillary ligand in the physical chemistry properties, cytotoxicity and mechanism of biological action. Neutral complexes, especially those bearing phenylbenzimidazole (HL1 and HL2), restrict the binding to DNA and albumin. One of them, complex 1[C,NH-Cl], is the most selective one, does not bind DNA, targets exclusively the mitochondria, disturbs the mitochondria membrane permeability inducing proton leak and increases ROS levels, triggering the molecular machinery of regulated cell death. In mice with orthotopic lung tumors, the administration of complex 1[C,NH-Cl] reduced the tumor burden. Cancers are more vulnerable than normal tissues to a treatment that harnesses mitochondrial dysfunction. Thus, complex 1[C,NH-Cl] characterization opens the way to the development of new compounds to exploit this vulnerability. Full article

(This article belongs to the Special Issue Advances in Anticancer Drugs and Pharmacotherapy of Cancer)

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Open AccessArticle

Efficient Synthesis with Green Chemistry Approach of Novel Pharmacophores of Imidazole-Based Hybrids for Tumor Treatment: Mechanistic Insights from In Situ to In Silico

Shaikh Mizanoor Rahman

Mohammad Khalid

Ajmal Khan

and

Ahmed Al-Harrasi

Cancers 2022, 14(20), 5079; https://doi.org/10.3390/cancers14205079 - 17 Oct 2022

Cited by 1 | Viewed by 679

Abstract

Imidazole-based pyrimidine hybrids are considered a remarkable class of compounds in pharmaceutical chemistry. Here, we report the anticancer bioactivities of eleven imidazole-based pyrimidine hybrids (1–11) that specifically target cytosolic carbonic anhydrase (CAs) isoenzymes, including human CA-II and human CA-IX (hCA-II, and hCA-IX). A highly eco-friendly aqueous approach was used for the formation of a carbon–carbon bond by reacting aromatic nitro group substitution of nitroimidazoles with carbon nucleophiles. The in vitro results indicate that this new class of compounds (1–11) includes significant inhibitors of hCA IX with IC₅₀ values in the range of 9.6 ± 0.2–32.2 ± 1.0 µM, while hCA II showed IC₅₀ values in range of 11.6 ± 0.2–31.1 ± 1.3 µM. Compound 2 (IC₅₀ = 12.3 ± 0.1 µM) showed selective inhibition for hCA-II while 7, 8, and 10 (IC₅₀ = 9.6–32.2 µM) were selective for hCA-IX. The mechanism of action was investigated through in vitro kinetics studies that revealed that compounds 7, 3, 11, 10, 4, and 9 for CA-IX and 1, 2, and 11 for CA-II are competitive inhibitors with dissociation constant (Ki) in the range of 7.32–17.02 µM. Furthermore, the in situ cytotoxicity of these compounds was investigated in the human breast cancer cell line MDA-MB-231 and compared with the normal human breast cell line, MCF-10A. Compound 5 showed excellent anticancer/cytotoxic activity in MDA-MB-231 with no toxicity to the normal breast cells. In addition, in silico molecular docking was employed to predict the binding mechanism of active compounds with their targets. This in silico observation aligned with our experimental results. Our findings signify that imidazole-based hybrids could be a useful choice to design anticancer agents for breast and lung tumors, or antiglaucoma compounds, by specific inhibition of carbonic anhydrases. Full article

(This article belongs to the Special Issue Advances in Anticancer Drugs and Pharmacotherapy of Cancer)

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Review

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Open AccessReview

Evaluation of Delayed-Type Hypersensitivity to Antineoplastic Drugs—An Overview

and

Cancers 2023, 15(4), 1208; https://doi.org/10.3390/cancers15041208 - 14 Feb 2023

Viewed by 487

Abstract

Nowadays, clinical practice encounters the problem of delayed-type hypersensitivity (DTH) induced by several drugs. Antineoplastic treatments are among the drugs which show an elevated proportion of DHT reactions, leading to the worsening of patients’ quality of life. The range of symptoms in DHT reactions can vary from mild, such as self-limiting maculopapular eruptions, to severe, such as Stevens–Johnson Syndrome. The development of these reactions supposes a negative impact, not only by limiting patients’ quality of life, but also leading to economic loss due to market withdrawal of the affected drugs and high hospitalization costs. However, despite this problem, there are no available standard in vitro or in vivo methods that allow for the evaluation of the sensitizing potential of drugs in the preclinical phase. Therefore, the aim of this review is to summarize the skin reactions caused by the different antineoplastic families, followed by a comprehensive evaluation of the in vitro and in vivo methods used to detect DTHs and that could be suitable to test antineoplastic hypersensitivity reactions. Full article

(This article belongs to the Special Issue Advances in Anticancer Drugs and Pharmacotherapy of Cancer)

Open AccessReview

Seaweed-Derived Sulfated Polysaccharides; The New Age Chemopreventives: A Comprehensive Review

Prajna Paramita Bhuyan

Rabindra Nayak

Srimanta Patra

Hadi Sajid Abdulabbas

Mrutyunjay Jena

and

Biswajita Pradhan

Cancers 2023, 15(3), 715; https://doi.org/10.3390/cancers15030715 - 24 Jan 2023

Cited by 1 | Viewed by 609

Abstract

Seaweed-derived bioactive compounds are regularly employed to treat human diseases. Sulfated polysaccharides are potent chemotherapeutic or chemopreventive medications since it has been discovered. They have exhibited anti-cancer properties by enhancing immunity and driving apoptosis. Through dynamic modulation of critical intracellular signalling pathways, such as control of ROS generation and preservation of essential cell survival and death processes, sulfated polysaccharides’ antioxidant and immunomodulatory potentials contribute to their disease-preventive effectiveness. Sulfated polysaccharides provide low cytotoxicity and good efficacy therapeutic outcomes via dynamic modulation of apoptosis in cancer. Understanding how sulfated polysaccharides affect human cancer cells and their molecular involvement in cell death pathways will showcase a new way of chemoprevention. In this review, the significance of apoptosis and autophagy-modulating sulfated polysaccharides has been emphasized, as well as the future direction of enhanced nano-formulation for greater clinical efficacy. Moreover, this review focuses on the recent findings about the possible mechanisms of chemotherapeutic use of sulfated polysaccharides, their potential as anti-cancer drugs, and proposed mechanisms of action to drive apoptosis in diverse malignancies. Because of their unique physicochemical and biological properties, sulfated polysaccharides are ideal for their bioactive ingredients, which can improve function and application in disease. However, there is a gap in the literature regarding the physicochemical properties and functionalities of sulfated polysaccharides and the use of sulfated polysaccharide-based delivery systems in functional cancer. Furthermore, the preclinical and clinical trials will reveal the drug’s efficacy in cancer. Full article

(This article belongs to the Special Issue Advances in Anticancer Drugs and Pharmacotherapy of Cancer)

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Open AccessReview

Multifaceted Pharmacological Potentials of Curcumin, Genistein, and Tanshinone IIA through Proteomic Approaches: An In-Depth Review

Farheen Badrealam Khan

and

Cancers 2023, 15(1), 249; https://doi.org/10.3390/cancers15010249 - 30 Dec 2022

Viewed by 1064

Abstract

Phytochemicals possess various intriguing pharmacological properties against diverse pathological conditions. Extensive studies are on-going to understand the structural/functional properties of phytochemicals as well as the molecular mechanisms of their therapeutic function against various disease conditions. Phytochemicals such as curcumin (Cur), genistein (Gen), and tanshinone-IIA (Tan IIA) have multifaceted therapeutic potentials and various efforts are in progress to understand the molecular dynamics of their function with different tools and technologies. Cur is an active lipophilic polyphenol with pleiotropic function, and it has been shown to possess various intriguing properties including antioxidant, anti-inflammatory, anti-microbial, anticancer, and anti-genotoxic properties besides others beneficial properties. Similarly, Gen (an isoflavone) exhibits a wide range of vital functions including antioxidant, anti-inflammatory, pro-apoptotic, anti-proliferative, anti-angiogenic activities etc. In addition, Tan IIA, a lipophilic compound, possesses antioxidant, anti-angiogenic, anti-inflammatory, anticancer activities, and so on. Over the last few decades, the field of proteomics has garnered great momentum mainly attributed to the recent advancement in mass spectrometry (MS) techniques. It is envisaged that the proteomics technology has considerably contributed to the biomedical research endeavors lately. Interestingly, they have also been explored as a reliable approach to understand the molecular intricacies related to phytochemical-based therapeutic interventions. The present review provides an overview of the proteomics studies performed to unravel the underlying molecular intricacies of various phytochemicals such as Cur, Gen, and Tan IIA. This in-depth study will help the researchers in better understanding of the pharmacological potential of the phytochemicals at the proteomics level. Certainly, this review will be highly instrumental in catalyzing the translational shift from phytochemical-based biomedical research to clinical practice in the near future. Full article

(This article belongs to the Special Issue Advances in Anticancer Drugs and Pharmacotherapy of Cancer)

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Open AccessReview

Targeting mTOR as a Cancer Therapy: Recent Advances in Natural Bioactive Compounds and Immunotherapy

Mohammed Merae Alshahrani

Ahmed Abdullah Al Awadh

and

Cancers 2022, 14(22), 5520; https://doi.org/10.3390/cancers14225520 - 10 Nov 2022

Cited by 1 | Viewed by 1595

Abstract

The mammalian target of rapamycin (mTOR) is a highly conserved serine/threonine-protein kinase, which regulates many biological processes related to metabolism, cancer, immune function, and aging. It is an essential protein kinase that belongs to the phosphoinositide-3-kinase (PI3K) family and has two known signaling complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). Even though mTOR signaling plays a critical role in promoting mitochondria-related protein synthesis, suppressing the catabolic process of autophagy, contributing to lipid metabolism, engaging in ribosome formation, and acting as a critical regulator of mRNA translation, it remains one of the significant signaling systems involved in the tumor process, particularly in apoptosis, cell cycle, and cancer cell proliferation. Therefore, the mTOR signaling system could be suggested as a cancer biomarker, and its targeting is important in anti-tumor therapy research. Indeed, its dysregulation is involved in different types of cancers such as colon, neck, cervical, head, lung, breast, reproductive, and bone cancers, as well as nasopharyngeal carcinoma. Moreover, recent investigations showed that targeting mTOR could be considered as cancer therapy. Accordingly, this review presents an overview of recent developments associated with the mTOR signaling pathway and its molecular involvement in various human cancer types. It also summarizes the research progress of different mTOR inhibitors, including natural and synthetised compounds and their main mechanisms, as well as the rational combinations with immunotherapies. Full article

(This article belongs to the Special Issue Advances in Anticancer Drugs and Pharmacotherapy of Cancer)

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Open AccessSystematic Review

Role of Immunotherapy in the Treatment of Cancer: A Systematic Review

Sia Pei Ling

Long Chiau Ming

Jagjit Singh Dhaliwal

and

Cancers 2022, 14(21), 5205; https://doi.org/10.3390/cancers14215205 - 24 Oct 2022

Viewed by 1337

Abstract

Tremendous progress has been made in cancer research over the years, and, as a result, immunotherapy has emerged as an important therapy for the treatment of cancer, either as a stand-alone treatment or in conjunction with other cancer therapies. Immunotherapy has demonstrated encouraging outcomes and offers a viable strategy for not only enhancing the quality of life but also dramatically boosting the overall survival rate of cancer patients. The objective of this systematic review was to assess the efficacy of immunotherapy in the treatment of cancer. Databases such as PubMed and Science Direct were searched from their inception until September 2021, using the following keywords: cancer immunotherapy, cancer recurrence, cancer treatment options, and cancer therapies. The systematic review was conducted in accordance with the PRISMA protocol. There were a total of 599 articles; however, after applying the inclusion and exclusion criteria, the final review ended up with 34 publications. In conclusion, the studies have demonstrated that immunotherapy is a viable alternative treatment option for patients with recurrent or metastatic cancer, since the overall survival rate and progression-free survival rate were shown to be successful. Full article

(This article belongs to the Special Issue Advances in Anticancer Drugs and Pharmacotherapy of Cancer)

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