Oxidative Stress and Cancer: The role of Nrf2.
Abstract Oxidative stress due to imbalance between ROS production and detoxification plays the pivotal role in determining cell fate. In response to excessive ROS, apoptotic signaling pathway is activated to promote normal cell death. However, through deregulation of biomolecules, high amount of ROS promotes carcinogenesis in cells with defective signaling factors. In this line, NRF2 appears to be as the master regulator to protect cells from oxidative and electrophilic stress. Nrf2 is an intracellular transcription factor that regulates the expression of a number of genes to encode anti-oxidative enzymes, detoxif...
Source: Current Cancer Drug Targets - October 2, 2017 Category: Cancer & Oncology Authors: Sajadimajd S, Khazaei M Tags: Curr Cancer Drug Targets Source Type: research

Ponatinib: A Review of Efficacy and Safety.
Abstract Ponatinib is a third generation kinase inhibitor designed to overcome the gatekeeper T315I mutation. In different trials this drug showed inhibitory activity against native BCR-ABL1 kinase and several ABL1 mutations. For this reason, ponatinib is currently indicated for the treatment of chronic myeloid leukaemia (CML) in every phase of disease resistant and/or intolerant to dasatinib and nilotinib and for whom imatinib is not indicated anymore or for patients with T315I mutation. The drug is also indicated for Ph+ acute lymphoblastic leukaemia (ALL). Ponatinib was temporarily suspended in 2013 for the occ...
Source: Current Cancer Drug Targets - October 2, 2017 Category: Cancer & Oncology Authors: Massaro F, Molica M, Breccia M Tags: Curr Cancer Drug Targets Source Type: research

The PI3K pathway at the crossroads of cancer and the immune system: strategies for next generation immunotherapy combinations.
Abstract Immunotherapy has led to a paradigm shift in the treatment of some malignancies, providing long-term, durable responses for a subset of patients with advanced cancers. Increasingly, research has identified links between the immune system and critical oncogenic growth factor pathways. The phosphoinositide 3-kinase (PI3K)-AKT-mTOR cascade is frequently hyperactivated in cancer, and plays an integral role in many cellular processes including tumour growth and survival and can underlie resistance to therapies. In this review, we first summarize two key learnings from the initial studies of inhibitors of this ...
Source: Current Cancer Drug Targets - September 26, 2017 Category: Cancer & Oncology Authors: Collins D, Chenard-Poirier M, Lopez J Tags: Curr Cancer Drug Targets Source Type: research

Neoisoliquiritigenin inhibits tumor progression by targeting GRP78- β-catenin signaling in breast cancer.
In this study, we found that GRP78 could promote breast cancer initiation and progression, and higher expression of GRP78 indicated poorer state of breast cancer patients, suggesting that GRP78 was a significant oncogene with the potential to be a novel biomarker and target in clinical investigation. Also, according to the analysis of molecular docking, we found a derivative of Isoliquiritigenin, Neoisoliquiritigenin (NISL), showed a vital inhibitory effect on breast cancer through direct binding to GRP78 to regulate β-catenin pathway. Taken together, this study not only highlight the significance of GRP78 in breast c...
Source: Current Cancer Drug Targets - September 14, 2017 Category: Cancer & Oncology Authors: Tang H, Peng F, Huang X, Xie X, Chen B, Shen J, Gao F, You J, Xie X, Chen J Tags: Curr Cancer Drug Targets Source Type: research

Coinhibitory molecule PD-1 as a therapeutic target in the microenvironment of Multiple Myeloma.
r N Abstract Immunological dysfunction in the microenvironment of multiple myeloma is a potential target for immune-mediated therapies. The programmed death 1 (PD-1) receptor is expressed on the surface of exhausted T and B cells and its ligand PD-L1 is expressed on tumor cells and inhibits T-cell-mediated apoptosis. Inhibiting such "checkpoint" by monoclonal antibodies recently has been shown high activity in solid tumors and malignant lymphomas. In patients with multiple myeloma PD-L1 is overexpressed on myeloma cells and PD1 on T-cells suggesting an active role of PD- 1/PD-L1 in the immunosuppressive ...
Source: Current Cancer Drug Targets - September 6, 2017 Category: Cancer & Oncology Authors: Atanackovic D, Luetkens T, Steinbach M, Kröger N Tags: Curr Cancer Drug Targets Source Type: research

Editorial: Signalling Pathways in Virus-caused Cancers.
PMID: 28828977 [PubMed - in process] (Source: Current Cancer Drug Targets)
Source: Current Cancer Drug Targets - August 24, 2017 Category: Cancer & Oncology Authors: Chen J Tags: Curr Cancer Drug Targets Source Type: research

Involvement of CD24 in Multiple Cancer Related Pathways Makes It an Interesting New Target for Cancer Therapy.
Abstract CD24 (cluster of differentiation 24) is a small heavy glycosylated protein, which is overexpressed in many cancer and some cancer stem cells and is associated with the development, invasion, and metastasis of cancer cells. The exact role of CD24 in these processes is not fully understood, however, in this article, it has been tried to present collection of cancer-related mechanisms attributed to CD24. Based on the literature, CD24 dis-regulates different signaling pathways in various cancer cells, including; Src kinases, STAT3, EGFR, Wnt/β-catenin and MAPK. Src kinases play an important role in the s...
Source: Current Cancer Drug Targets - August 18, 2017 Category: Cancer & Oncology Authors: Eyvazi S, Kazemi B, Dastmalchi S, Bandehpour M Tags: Curr Cancer Drug Targets Source Type: research

Clinical evidence on the magnitude of change in growth pathway activity in relation to Tamoxifen resistance is required.
CONCLUSION: Although clinical findings regarding the molecular pathways downstream of RTKs have been thoroughly discussed in this review, further clinical studies are required in determining a consistency between preclinical and clinical findings. Discovering the best targets in preventing tumor progression requires thorough comprehension of estrogen-dependent and estrogen-independent pathways during Tamoxifen resistance development. Indeed, exploring additional clinically-proven targets would allow for better characterized treatments being available for breast cancer patients. PMID: 28786348 [PubMed - as supplied by ...
Source: Current Cancer Drug Targets - August 8, 2017 Category: Cancer & Oncology Authors: Mansouri S, Farahmand L, Teymourzadeh A, Majidzadeh-A K Tags: Curr Cancer Drug Targets Source Type: research

Aldose reductase inhibitor, fidarestat prevents high-fat diet-induced intestinal polyps in ApcMin/+ mice.
CONCLUSION: Our results thus suggest that fidarestat could be used as a potential chemopreventive drug for intestinal cancers due to APC gene mutations. PMID: 28786349 [PubMed - as supplied by publisher] (Source: Current Cancer Drug Targets)
Source: Current Cancer Drug Targets - August 8, 2017 Category: Cancer & Oncology Authors: Saxena A, Tammali R, Ramana KV, Srivastava SK Tags: Curr Cancer Drug Targets Source Type: research

TGF- β1 Causes EMT by regulating N-Acetyl Glucosaminyl Transferases via Downregulation of Non Muscle Myosin II-A through JNK/P38/PI3K pathway in lung cancer.
CONCLUSION: The study reports a novel pathway through which NMII-A negatively regulates EMT and metastasis via up regulation of C2GnT-M, GnT-V and down expression of GnT-III. These findings of lung cancer may further be required to study in other cancer types. PMID: 28782471 [PubMed - as supplied by publisher] (Source: Current Cancer Drug Targets)
Source: Current Cancer Drug Targets - August 7, 2017 Category: Cancer & Oncology Authors: Khan GJ, Gao Y, Gu M, Wang L, Khan S, Naeem F, Yousef BA, Roy D, Semukunzi H, Yuan S, Sun L Tags: Curr Cancer Drug Targets Source Type: research

Cell-derived Exosomes as Promising Carriers for Drug Delivery and Targeted Therapy.
Abstract Exosomes are small vesicles that are secreted by various types of cells, known to mediate signal transduction between cells. During recent years, novel carriers for the delivery of targeted drugs, chemotherapy drugs and RNAs are under development, which is believed to be beneficial for patients. Considering issues of drug nano-formulations in bloodstream, such as nano-toxicity and rapid clearance by mononuclear phagocyte system, exosomes derived from either patient's cells or bodyfluids, seem to be an optimal option. This review presents the current patterns of drug-loaded into exosomes and discuss how ex...
Source: Current Cancer Drug Targets - July 10, 2017 Category: Cancer & Oncology Authors: Wang X, Zhang H, Yang H, Bai M, Ning T, Li S, Li J, Deng T, Ying G, Ba Y Tags: Curr Cancer Drug Targets Source Type: research

The Safety, Efficacy and Therapeutic Potential of Histone Deacetylase Inhibitors with Special Reference to Panobinostat in Gastrointestinal Tumors: A Review of Preclinical and Clinical Studies.
Abstract Histone deacetylase inhibitors (HDACi) have demonstrated as an emerging class of anticancer drugs involved in regulation of gene expression and chromatin remodeling thus indicating valid targets for different types of cancer therapeutics. The pan-deacetylase inhibitor panobinostat (Farydac®, LBH589) is developed by Novartis Pharmaceuticals and a newly US FDA approved drug for the multiple myeloma. It is under clinical investigation for a range of hematological and solid tumors worldwide in both oral and intravenous formulations. Panobinostat inhibits tumor cell growth by interacting with acetylation o...
Source: Current Cancer Drug Targets - June 30, 2017 Category: Cancer & Oncology Authors: Singh A, Patel P, Jageshwar, Patel VK, Jain DK, Kamal M, Rajak H Tags: Curr Cancer Drug Targets Source Type: research

Synthetic lethality: From Research to Precision Cancer Nanomedicine.
Abstract Cancer is an evolutionary disease with multiple genetic alterations, accumulated due to chromosomal instability and/or aneuploidy and it sometimes acquires drug-resistant phenotype also. Whole genome sequencing and mutational analysis helped in understanding the differences among persons for predisposition of a disease and its treatment non-responsiveness. Thus, molecular targeted therapies came into existence. Among them, the concept of synthetic lethality have enthralled great attention as it is a pragmatic approach towards exploiting cancer cell specific mutations to specifically kill cancer cells with...
Source: Current Cancer Drug Targets - June 30, 2017 Category: Cancer & Oncology Authors: Gupta A, Ahmad A, Dar AI, Khan R Tags: Curr Cancer Drug Targets Source Type: research

MicroRNA Key to Angiogenesis Regulation: miRNA Biology and Therapy.
Abstract Angiogenesis is involved in maintaining normal physiological processes like embryonic development, wound healing, inflammation and reproduction. Pathogenesis of various diseases like diabetic retinopathy, rheumatoid arthritis and cancer are associated with imbalanced angiogenesis. Angiogenic stimulators and inhibitors act together for keeping angiogenic switch in balance. Recently miRNAs have been found to regulate various stages of angiogenesis. miRNAs are 21-23 nucleotides long, single stranded, noncoding RNA molecules generated endogenously. miRNA's ability to target multiple genes within a signaling p...
Source: Current Cancer Drug Targets - June 30, 2017 Category: Cancer & Oncology Authors: Tiwari A, Mukherjee B, Dixit M Tags: Curr Cancer Drug Targets Source Type: research

DNA fragmentation, cell cycle arrest, and docking study of novel bis spiro-cyclic 2-oxindole of pyrimido[4,5-b]quinoline-4,6-dione derivatives against breast carcinoma.
Abstract An efficient one pot synthesis of bis spiro-cyclic 2-oxindole derivatives of pyrimido[4,5-b]quinoline-4,6-dione using 6-aminouracil, bis-isatin and dimedone has been developed. The cytotoxic effect against different human cell lines MCF7, HCT116 and A549 cell lines was evaluated. The derivative 6a, was found the most encouraging compound in this series and it was selected for molecular studies against MCF7. Our data indicated that compound 6a is an attractive target for breast cancer, as it inhibits proliferation, cell cycle progression and induces apoptosis of tumor cells. This inhibition is mediated by ...
Source: Current Cancer Drug Targets - June 30, 2017 Category: Cancer & Oncology Authors: Mohamed MF, Abdelmoniem AM, Elwahy AHM, Abdelhamid IA Tags: Curr Cancer Drug Targets Source Type: research

Oncolytic tanapoxvirus expressing interleukin-2 is capable of inducing the regression of human melanoma tumors in the absence of T cells.
In this study, a recombinant TANV expressing mouse IL-2 (TANVΔ66R/mIL-2) was generated, where the viral thymidine kinase (TK) gene (66R) was replaced with the mIL-2 transgene. In cell culture, expression of IL-2 attenuated virus replication of not only TANVΔ66R/mIL-2, but also TANVGFP when co-infecting with TANVΔ66R/mIL-2. Further, we demonstrate that IL-2 inhibits virus replication through intracellular components and without activating the interferon-signaling pathway. The anti-tumor potential of TANVΔ66R/mIL-2 was studied in athymic nude mice carrying human melanoma xenografts. Introduction of mI...
Source: Current Cancer Drug Targets - June 30, 2017 Category: Cancer & Oncology Authors: Zhang T, Kordish DH, Suryawanshi YR, Eversole RR, Kohler S, Mackenzie CD, Essani K Tags: Curr Cancer Drug Targets Source Type: research

Therapeutic approaches for the treatment of epidermal growth factor receptor mutated lung cancer.
This article presents a detailed molecular insight of the therapeutic approaches for the treatment of EGFR mutant lung cancer. The article delineates molecular mechanism of the drugs that are approved, the drugs that are in clinical trial and the drugs that have not entered a clinical trial but shows promising future in the treatment of EGFR mutant lung cancer. Furthermore, this article provides concise information on relevant combinational or monotherapy clinical trials that have been completed for various approaches. PMID: 28669334 [PubMed - as supplied by publisher] (Source: Current Cancer Drug Targets)
Source: Current Cancer Drug Targets - June 23, 2017 Category: Cancer & Oncology Authors: Sanchala D, Bhatt LK, Prabhavalkar KS Tags: Curr Cancer Drug Targets Source Type: research

Regulation of microRNAs by phytochemicals: a promising strategy for cancer chemoprevention.
Abstract A growing body of evidence suggests that phytochemicals are potentially able to affect a variety of cellular processes, including proliferation, apoptosis, cell-cycle control, angiogenesis, inflammation, and DNA repair. Phytochemicals typically play pleiotropic regulatory roles in cancer cells. Chemoprevention using these natural agents has emerged as a helpful strategy to manage a variety of malignancies. With regard to cancer-associated chemopreventive mechanisms, phytochemicals can act by modulating microRNAs (miRNAs) and their target genes. This review aims to present an overview of recent findings on...
Source: Current Cancer Drug Targets - June 23, 2017 Category: Cancer & Oncology Authors: Babashah S, Bakhshinejad B, Birgani MT, Pakravan K, Cho WC Tags: Curr Cancer Drug Targets Source Type: research

JQ1, a BET inhibitor, synergizes with cisplatin and induces apoptosis in highly chemoresistant malignant pleural mesothelioma cells.
Abstract Malignant pleural mesothelioma (MPM) is an asbestos-associated tumor with poor prognosis and few therapeutic options. JQ1, a selective antagonist of BRD4, modulates transcription of oncogenes, including MPM chemoresistance-associated c-Myc and Fra-1. We investigated if JQ1 could enhance the efficacy of cisplatin against MPM. The antiproliferative activity of cisplatin in combination with JQ1 was assessed on MPM cell lines representative of the cellular phenotypes of this tumor (epithelioid, sarcomatoid and biphasic), and on one cisplatin-resistant sub-line (established in our laboratory). The combination ...
Source: Current Cancer Drug Targets - June 23, 2017 Category: Cancer & Oncology Authors: Zanellato I, Colangelo D, Osella D Tags: Curr Cancer Drug Targets Source Type: research

Chemosensitizing activity of histone deacetylases inhibitory cyclic hydroxamic acids for combination chemotherapy of lymphatic leukemia.
Abstract Chemosensitizing properties of water soluble cyclic hydroxamic acids (CHA) prepared from Glycine (a), Alanine (b), Valine (c), Leucine (d), and Phenylalanine (e) hydroxamic acids and α-biperidones-4 are evaluated using in vitro activities and in vivo methods and found significant results. These compounds possess iron(II) chelating properties, and slightly inhibit lipid peroxidation. CHA prepared from triacetonamine (1a-e) are more effective Fe (II) ions chelators, as compared to CHA prepared from 1-methylpiperidone (2a-e). The histone deacetylase (HDAC) inhibitory activity, lipophilicity and acute t...
Source: Current Cancer Drug Targets - June 23, 2017 Category: Cancer & Oncology Authors: Mishchenko DV, Neganova ME, Klimanova EN, Sashenkova TE, Shevtsova EF, Vystorop IV, Tarasov VV, Ashraf GM, Yarla NS, Aliev G Tags: Curr Cancer Drug Targets Source Type: research

Pharmacoinformatic Approaches to Design Novel Inhibitors of Protein Kinase B Pathways in Cancer.
CONCLUSION: Isoform selective inhibition of Akt might have clinical significance and thus, should be taken into account in future investigations. Moreover, an up to date isoform selective chemical data is required to further validate already reported isoform selective binding hypothesis. PMID: 28669343 [PubMed - as supplied by publisher] (Source: Current Cancer Drug Targets)
Source: Current Cancer Drug Targets - June 23, 2017 Category: Cancer & Oncology Authors: Akhtar N, Jabeen I Tags: Curr Cancer Drug Targets Source Type: research

p53-Mdm2 interaction inhibitors as novel nongenotoxic anticancer agents.
CONCLUSION: Agents designed to block the p53-Mdm2 interaction may have a therapeutic potential for treatment of a subset of human cancers retaining wild-type p53. We review herein the recent advances in the design and development of potent small molecules as p53-Mdm2 inhibitors. PMID: 28669344 [PubMed - as supplied by publisher] (Source: Current Cancer Drug Targets)
Source: Current Cancer Drug Targets - June 23, 2017 Category: Cancer & Oncology Authors: Nayak SK, Khatik GL, Narang R, Monga V, Chopra HK Tags: Curr Cancer Drug Targets Source Type: research

Significant role of MUC1 in development of resistance to currently existing anti-cancer therapeutic agents.
Abstract As an extensively glycosylated transmembrane protein of epithelium, Mucin1 (MUC1) mostly protects cells from tensions induced by external milieu. Physiologically, during stress condition, MUC1 separates into MUC1-N and MUC1-C moieties, resulting in transduction of inward survival signals, essential for maintaining cell's functionality. Recent studies have proposed a significant correlation between MUC1 overexpression and amplification of cancer cell's proliferation and metastasis through modulation of multiple signaling pathways and cell-cell and cell-matrix interactions. It has been shown that MUC1- Cyto...
Source: Current Cancer Drug Targets - June 23, 2017 Category: Cancer & Oncology Authors: Farahmand L, Merikhian P, Jalili N, Darvishi B, Majidza K Tags: Curr Cancer Drug Targets Source Type: research

Crizotinib versus chemotherapy on ALK-positive NSCLC :a systematic review of efficacy and safety.
Abstract Introduction Crizotinib was approved to treat anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) by the Food and Drug Administration in 2011.We conducted a systematic review of clinical trials and retrospective studies to compare the efficacy and safety of crizotinib with chemotherapy. Methods We searched electronic databases from inception to Dec. 2016. Clinical trials and retrospective studies regarding crizotinib and crizotinib versus chemotherapy in treatment of NSCLC were eligible. The primary outcome were the objective response rate (ORR) and disease control rate (DCR). Res...
Source: Current Cancer Drug Targets - June 23, 2017 Category: Cancer & Oncology Authors: Wang M, Wang G, Ma H, Shan B Tags: Curr Cancer Drug Targets Source Type: research

Evaluation of anti-cancer activity of stilbene and methoxydibenzo[b,f]oxepin derivatives.
CONCLUSIONS: Among newly synthesized stilbene derivatives we selected two as potent anticancer compounds triggering late apoptosis/necrosis in cancerous cells through sub-G1 phase cell cycle arrest. They changed cyclin expression, induced DNA repair mechanisms, enzymes involved in apoptosis, and oxidative stress response. Compounds JJR5 and JJR6 can be a base for structure modification(s) to obtain even more active derivatives. PMID: 28669347 [PubMed - as supplied by publisher] (Source: Current Cancer Drug Targets)
Source: Current Cancer Drug Targets - June 23, 2017 Category: Cancer & Oncology Authors: Garbicz D, Mielecki D, Wrzesiński M, Pilżys T, Marcinkowski M, Piwowarski J, Dębski J, Palak E, Szczeciński P, Krawczyk H, Grzesiuk E Tags: Curr Cancer Drug Targets Source Type: research

The Structural Bioinformatics analysis of Biophenolic Lignan-Estrogen Receptor interaction.
CONCLUSION: Among the studied lignans, matairesinol showed the least binding energy as well as the most similar hydrophobic interactions to tamoxifen suggesting that matairesinol can display more efficacious biological activity to inhibit ER in comparison with pinoresinol, lariciresinol and secoisolariciresinol. Thus, our results introduce matairesinol as a potentially effective anti-ER drug. PMID: 28669348 [PubMed - as supplied by publisher] (Source: Current Cancer Drug Targets)
Source: Current Cancer Drug Targets - June 23, 2017 Category: Cancer & Oncology Authors: Mohamadyar-Toupkanlou F, Esfandiari M, Kashef-Saberi MS, Renani MK, Soleimani M Tags: Curr Cancer Drug Targets Source Type: research

Recent Updates on the Therapeutic Potential of HER2 Tyrosine Kinase Inhibitors for the Treatment of Breast Cancer.
Abstract HER2 positive breast cancer is characterized by the low survival rate in the metastatic patients. Development of resistance and disease-relapse are the major problems associated with the currently available therapies for HER2 positive breast cancer. There are two major targeted therapies for HER2 positive breast cancer viz. monoclonal antibodies and tyrosine-kinase inhibitors, and both of these therapies have their advantages and limitations. To address the limitations associated with the existing therapies, use of antibodies and TKIs as combination therapy proved to be more effective. Various chemical mo...
Source: Current Cancer Drug Targets - June 23, 2017 Category: Cancer & Oncology Authors: Singla H, Munshi A, Banipal RPS, Kumar V Tags: Curr Cancer Drug Targets Source Type: research

Fertility drugs and ovarian cancer.
Abstract The aetiology of ovarian cancer is multifactorial with both endogenous and exogenous risk factors playing an important role. The exact pathogenesis of ovarian cancer is still not well understood, despite the number of hypotheses published. Due to an increase in the number of women using fertility drugs, much attention has been focused on the long-term health effects of such drugs. Although fertility drugs facilitate the ovulation process, it is however associated with a significant increase in hormone concentrations, placing exposed women at increased risk of gynaecological cancer. Many clinical and epide...
Source: Current Cancer Drug Targets - June 20, 2017 Category: Cancer & Oncology Authors: Ali AT Tags: Curr Cancer Drug Targets Source Type: research

The Complexity of DEK Signaling in Cancer Progression.
Abstract The DNA binding protein and chromatin structural regulator DEK regulates many cellular processes. These include proliferation, differentiation, apoptosis, senescence, DNA repairing and the maintenance of stem cell phenotype. DEK is increasingly recognized as a crucial player in many steps of cancer initiation and progression, and is precisely regulated by abundant promoting and inhibiting factors directly or indirectly. DEK may serve as an architectural modulating protein to regulate the expression and function of multiple human genes in cancer cells. In this article we have reviewed the specificities and...
Source: Current Cancer Drug Targets - May 21, 2017 Category: Cancer & Oncology Authors: Teng Y, Lang L, Jauregui CE Tags: Curr Cancer Drug Targets Source Type: research

Cancer-targeted oncolytic adenoviruses for modulation of the immune system.
minki A Abstract Adenovirus is one of the most commonly used vectors for gene therapy and it is the first approved virus-derived drug for treatment of cancer. As an oncolytic agent, it can induce lysis of infected cells, but it can also engage the immune system, promoting activation and maturation of antigen-presenting cells (APCs). In essence, oncolysis combined with the associated immunostimulatory actions result in a "personalized in situ vaccine" for each patient. In order to take full advantage of these features, we should try to understand how adenovirus interacts with the immune system, what are t...
Source: Current Cancer Drug Targets - May 2, 2017 Category: Cancer & Oncology Authors: Cerullo V, Capasso C, Vähä-Koskela M, Hemminki O, Hemminki A Tags: Curr Cancer Drug Targets Source Type: research

Epithelial-to-Mesenchymal Transition: a Mediator of Sorafenib Resistance in Advanced Hepatocellular Carcinoma.
Abstract Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide and its incidence is steadily rising. Currently, sorafenib remains the only approved standard treatment for patients with advanced HCC, as it has proven to increase survival in these patients. However, clinical and preclinical observations indicate that sorafenib treatment may have limited efficacy due to tumor progression from the rapid development of acquired resistance. Elucidation of the underlying mechanisms of evasive resistance to sorafenib is a major challenge in HCC research. In recent years, the role of epithelial-to-mese...
Source: Current Cancer Drug Targets - April 26, 2017 Category: Cancer & Oncology Authors: Mir N, Jayachandran A, Dhungel B, Shrestha R, Steel JC Tags: Curr Cancer Drug Targets Source Type: research

Impact of IL-12 in cancer.
CONCLUSION: IL-12 has potential roles in anticancer therapy. The advantages of using immunotherapeutic approaches in clinical trials have been reported recently. However, the mechanisms to underlay the immunoregulation and antitumor activities of IL-12 itself, as well as its combination, remain under investigation. PMID: 28460617 [PubMed - as supplied by publisher] (Source: Current Cancer Drug Targets)
Source: Current Cancer Drug Targets - April 26, 2017 Category: Cancer & Oncology Authors: Lu X Tags: Curr Cancer Drug Targets Source Type: research

Specific targeting of HER2-positive head and neck squamous cell carcinoma line HN5 by Idarubicin-ZHER2 affibody conjugate.
In conclusion, idarubicin-ZHER2 affibody conjugate in optimum concentrations can be used for specific targeting and killing of HN5 cells. PMID: 28460618 [PubMed - as supplied by publisher] (Source: Current Cancer Drug Targets)
Source: Current Cancer Drug Targets - April 26, 2017 Category: Cancer & Oncology Authors: Ghanemi M, Pourshohod A, Ghaffari MA, Kheirollah A, Amin M, Zeinali M, Jamalan M Tags: Curr Cancer Drug Targets Source Type: research

Targeting STEAP1 protein in human cancer: current trends and future challenges.
aia C Abstract Cancer is a global health issue that impairs the life quality of patients and origins thousands of deaths annually worldwide. Six-transmembrane epithelial antigen of the prostate (STEAP1) was identified to be overexpressed in several types of cancers, namely in prostate cancer (PCa). Considering its secondary structure, associated with its location in the cell membrane, has been suggested a role in intercellular communication between tumour cells. Taking into account its high specificity and overexpression in human cancers, STEAP1 is nowadays a promising candidate to be imposed as a therapeutic targ...
Source: Current Cancer Drug Targets - April 26, 2017 Category: Cancer & Oncology Authors: Barroca-Ferreira J, Pais JP, Santos MM, Gonçalves AM, Gomes IM, Sousa IM, Rocha SM, Passarinha LA, Maia C Tags: Curr Cancer Drug Targets Source Type: research

CX-4945, a selective inhibitor of casein kinase 2, synergizes with B cell receptor signaling inhibitors in inducing diffuse large B cell lymphoma cell death.
CONCLUSION: These findings suggest a role for CK2 downstream of the BCR in controlling survival pathways crucial for cell growth of different DLBCL subtypes. Also, the use of CX-4945 in combination with BCR signaling blockers could represent a novel rational therapeutic approach in DLBCL. PMID: 28460620 [PubMed - as supplied by publisher] (Source: Current Cancer Drug Targets)
Source: Current Cancer Drug Targets - April 26, 2017 Category: Cancer & Oncology Authors: Mandato E, Nunes SC, Zaffino F, Casellato A, Macaccaro P, Tubi LQ, Visentin A, Trentin L, Semenzato G, Piazza F Tags: Curr Cancer Drug Targets Source Type: research

Effects of PHA-665752 and cetuximab combination treatment on in vitro and murine xenograft growth of human colorectal cancer cells with KRAS or BRAF mutations.
CONCLUSION: Combination treatment with PHA-665752 and cetuximab suppressed in vitro and in vivo CRC cell growth more than treatment with either agent alone did. PMID: 28359236 [PubMed - as supplied by publisher] (Source: Current Cancer Drug Targets)
Source: Current Cancer Drug Targets - March 30, 2017 Category: Cancer & Oncology Authors: Jia YT, Yang DH, Zhao Z, Bi XH, Han WH, Feng B, Zhi J, Gu B, Duan Z, Wu JH, Ju YC, Wang MX, Li ZX Tags: Curr Cancer Drug Targets Source Type: research

Influence of Aldo-keto reductase 1C3 in prostate cancer -a mini review.
Abstract Aldo-keto reductase 1C3 (AKR1C3) is an important oxidoreductase with multiple substrates, that is involved in producing extra-testicular androgens. Its activity is influenced by environmental exposures, as well as by genetic variants. These genetic variants could therefore produce variable testosterone levels and subsequent androgen receptor (AR) activation. This could lead to differential downstream production of the prostate-specific antigen (PSA). As PSA level is used for clinical evaluation of the prostate, these variations could impact prostate cancer (PC) diagnosis, as well as PC management outcomes...
Source: Current Cancer Drug Targets - March 30, 2017 Category: Cancer & Oncology Authors: Karunasingh N, Masters J, Flanagan JU, Ferguson LR Tags: Curr Cancer Drug Targets Source Type: research

HR+, HER2- Advanced Breast Cancer and CDK4/6 Inhibitors: Mode of action, Clinical Activity, and Safety Profiles.
Abstract Cyclin-dependent kinase (CDK) 4/6 inhibitor-based therapies have shown great promise in improving clinical outcomes for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. Addition of a CDK4/6 inhibitor to endocrine therapy increases efficacy and delays disease progression. Successful use of CDK4/6 inhibitor-based therapies in the clinic requires insight into the unique side-effect profiles of this class of agents and effective patient monitoring. In this review, we discuss the mode of action of the three CDK4/6 inhibitors in lat...
Source: Current Cancer Drug Targets - March 30, 2017 Category: Cancer & Oncology Authors: Sammons SL, Topping DL, Blackwell KL Tags: Curr Cancer Drug Targets Source Type: research

Oncolytic Virotherapy and Gene Therapy Strategies for Hepatobiliary Cancers.
Abstract Advanced liver cancers and biliary cancers represent diseases with dismal prognosis because of frequent local invasion and metastasis. Effective therapeutic agents for these cancers have not been established. Oncolytic viruses (OVs) constitute a novel class of promising, selective anticancer agents and recent studies have elucidated their unique features. Moreover, clinical trials are demonstrating promising results. Numerous OVs are being tested in preclinical models of hepatocellular carcinoma (HCC). The lead agent Pexa-Vec (pexastimogene devacirepvec, JX-594) , a recombinant Wyeth strain vaccinia virus...
Source: Current Cancer Drug Targets - March 30, 2017 Category: Cancer & Oncology Authors: Yamada T, Hamano Y, Hasegawa N, Yokoyama KK, Hyodo I, Abei M Tags: Curr Cancer Drug Targets Source Type: research

Elaborating the role of natural products on the regulation of autophagy and their potentials in breast cancer therapy.
Abstract Autophagy is an intracellular lysosomal/vacuolar degradation system, which the inner cytoplasmic cell membrane is degraded by the lysosomal hydrolases, followed by the resulting products released back into the cytosol. It is involved in many physiological processes which are crucial for cell growth and survival. However, disturbance in the autophagic process is often associated with a variety of human diseases, such as cancer. Breast cancer is one of the most malignant tumors characterized by the imbalanced cell proliferation, apoptosis as well as disordered autophagy regulation. The alterations of autoph...
Source: Current Cancer Drug Targets - March 30, 2017 Category: Cancer & Oncology Authors: Zhou X, Yue GG, Tsui SK, Pu J, Fung KP, Lau CB Tags: Curr Cancer Drug Targets Source Type: research

Obesity and cancer: biological links and treatment implications.
Abstract Obesity is an epidemic disease and correlates with cardiovascular diseases increasing the overall mortality. However, it has been recently demonstrated that cancer is an unexpected consequence of obesity. In most of the studies it is evaluated with body mass index (BMI): high BMI increases cancer risk and reduces survival of many solid tumors. The main biologic and clinic topics regarding obese cancer patients are here presented and discussed. Hyperinsulinemia and Insulin-like Growth Factors (IGFs) are among the most important links between cancer and obesity. However, adipose tissue (AT) produces also se...
Source: Current Cancer Drug Targets - March 30, 2017 Category: Cancer & Oncology Authors: Ottaiano A, De Divitiis C, Capozzi M, Avallone A, Pisano C, Pignata S, Tafuto S Tags: Curr Cancer Drug Targets Source Type: research

Small-molecule inhibitors of epigenetic mutations as compelling drug-targets for myelodysplastic syndromes.
CONCLUSION: Mutation-specific targeted epigenetic drugs, which have already sensitized drug-makers and regulators, may promise attestation of 'del5q and lenalidomide'-like specific drugs for every mutational signature independently or in combination with standard therapeutic elements used for MDS-management, and that will add to understand their antagonistic/synergistic effects. PMID: 28359242 [PubMed - as supplied by publisher] (Source: Current Cancer Drug Targets)
Source: Current Cancer Drug Targets - March 30, 2017 Category: Cancer & Oncology Authors: Ganguly BB Tags: Curr Cancer Drug Targets Source Type: research

Redox biotransformation and delivery of anthracycline anticancer antibiotics: How interpretable structure-activity relationships of lethality using electrophilicity and the London formula for dispersion interaction work.
Abstract Quantum chemical methods and molecular mechanics approaches face a lot of challenges in drug metabolism study because of their either insufficient accuracy or huge computational cost, or lack of clear molecular level pictures for building computational models. Low-cost QSAR methods can often be carried out even though molecular level pictures are not well defined; however, they show difficulty in identifying the mechanisms of drug metabolism and delineating the effects of chemical structures on drug toxicity because a certain amount of molecular descriptors are difficult to be interpreted. In order to mak...
Source: Current Cancer Drug Targets - March 30, 2017 Category: Cancer & Oncology Authors: Pang SK Tags: Curr Cancer Drug Targets Source Type: research

Potential therapeutic targets in energy metabolism pathways of breast cancer.
Abstract Mutations in proto-oncogenes and tumor suppressor genes make cancer cells proliferate indefinitely. As they possess almost all mechanisms for cell proliferation and survival like healthy cells, it is difficult to specifically target cancer cells in the body. Current treatments in most of the cases are harmful to healthy cells as well. Thus, it would be of great prudence to target specific characters of cancer cells. Since cancer cells avidly use glucose and glutamine to survive and proliferate by upregulating the relevant enzymes and their specific isoforms having important regulatory roles, it has been o...
Source: Current Cancer Drug Targets - March 30, 2017 Category: Cancer & Oncology Authors: Islam RA, Hossain S, Chowdhury EH Tags: Curr Cancer Drug Targets Source Type: research

The β2-Adrenergic Agonist Salbutamol Inhibits Migration, Invasion and Metastasis of the Human Breast Cancer MDA-MB-231 Cell Line.
CONCLUSION: Our results suggest that salbutamol could be an effective adjuvant drug for the treatment of metastatic breast cancer. PMID: 28359245 [PubMed - as supplied by publisher] (Source: Current Cancer Drug Targets)
Source: Current Cancer Drug Targets - March 30, 2017 Category: Cancer & Oncology Authors: Rivero EM, Piñero CP, Gargiulo L, Entschladen F, Zänker K, Bruzzone A, Lüthy IA Tags: Curr Cancer Drug Targets Source Type: research

In-silico & In-vitro identification of structure-activity relationship pattern of Serpentine & Gallic acid targeting PI3K γ as potential anticancer target.
In-silico & In-vitro identification of structure-activity relationship pattern of Serpentine & Gallic acid targeting PI3Kγ as potential anticancer target. Curr Cancer Drug Targets. 2017 Mar 30;: Authors: Sharma P, Shukla A, Kalani K, Dubey V, Luqman S, Srivastava SK, Khan F Abstract Natural products showed anticancer activity and often induce apoptosis or autophagy in cancer cells through the PI3K/Akt/mTOR signaling pathways. The potential of natural products as PI3Ks inhibitors has been reported, which suggest PI3Ks a promising anticancer target. Phosphoinositide 3-kinase (PI3K) is a fa...
Source: Current Cancer Drug Targets - March 30, 2017 Category: Cancer & Oncology Authors: Sharma P, Shukla A, Kalani K, Dubey V, Luqman S, Srivastava SK, Khan F Tags: Curr Cancer Drug Targets Source Type: research

Method to Assess Interactivity of Drugs with Nonparallel Concentration-Effect Relationships.
CONCLUSION: UE is a broadly applicable method for analysis, including statistical significance assessment, of drug interactivity. PMID: 28359247 [PubMed - as supplied by publisher] (Source: Current Cancer Drug Targets)
Source: Current Cancer Drug Targets - March 30, 2017 Category: Cancer & Oncology Authors: Zhao L, Au JL, Wientjes MG Tags: Curr Cancer Drug Targets Source Type: research

Immunomodulatory activity of microRNAs: potential implications for multiple myeloma treatment.
one P Abstract Multiple myeloma (MM) is an incurable plasma cell neoplasm accounting for about 10% of all hematologic malignancies. Recently, emerging evidence is disclosing the complexity of bone marrow interactions between MM cells and infiltrating immune cells, which have been reported to promote proliferation, survival and drug resistance of tumor cells. MicroRNAs (miRNAs) are small non-coding RNA molecules with regulatory functions in the cell, whose expression has predictive and prognostic value in different malignancies. MiRNAs are gaining increasing interest due to their capability to polarize the immune-r...
Source: Current Cancer Drug Targets - March 30, 2017 Category: Cancer & Oncology Authors: Botta C, Cucè M, Caracciolo D, Fiorillo L, Tagliaferri P, Tassone P Tags: Curr Cancer Drug Targets Source Type: research

Autophagy Inhibition in Childhood Nephroblastoma and the Therapeutic Significance.
In this study, in clinical samples of childhood nephroblastoma, autophagy activity was evaluated by the expressions of selected autophagy markers as well as the presence of autophagosome ultrastructure. Decrease of Beclin 1 level and number of autophagosomes was found in nephroblastoma, suggesting autophagy inhibition. Furthermore, in two anaplastic nephroblastoma cell lines, G401 and SK-NEP1, autophagy inhibitors further enhanced the efficacy of conventional chemotherapeutics including vincristine and cisplatin. In G401 tumor model established in nude mice, combinational use of chloroquine, a inhibitor of autophagy degrad...
Source: Current Cancer Drug Targets - March 30, 2017 Category: Cancer & Oncology Authors: Li LJ, Wang YL, Yuan LQ, Gu WZ, Zhu K, Yang M, Zhou D, Lv Y, Li MJ, Zhao ZY, Wang JH, Chen X Tags: Curr Cancer Drug Targets Source Type: research

Insight into discovery of next generation reversible TMLR inhibitors targeting EGFR activating and drug resistant T790M mutants.
Abstract Cancer is one of the most challenging diseases among the various causes of deaths worldwide. Among cancer, lung cancer rules as the leading cause of cancer-related deaths annually.The majority of the lung cancers identified are non-small cell lung cancer (NSCLC). Clinically, the Epidermal Growth Factor Receptor (EGFR) is a therapeutically accepted target for NSCLC. Many therapeutic leads that target this transmembrane receptor protein were tested for anti-EGFR activity that led to the discovery of gefitinib and erlotinib. These ATP-competitive first generation EGFR inhibitors are the first-line treatment ...
Source: Current Cancer Drug Targets - March 30, 2017 Category: Cancer & Oncology Authors: Agarwal SM, Pal D, Gupta M, Saini R Tags: Curr Cancer Drug Targets Source Type: research