Generic placeholder image

Current Cancer Therapy Reviews

Editor-in-Chief

ISSN (Print): 1573-3947
ISSN (Online): 1875-6301

Review Article

Key Signaling Pathways Engaged in Cancer Management: Current Update

Author(s): Sanjiv Singh* and Rahul Shukla

Volume 16, Issue 1, 2020

Page: [36 - 48] Pages: 13

DOI: 10.2174/1573394714666180904122412

Price: $65

Abstract

Background: Till today cancer is still challenging to treat and needs more active therapeutic approaches. Participation of complex multi-pathway cell propagation instrument is a noteworthy issue in creating active anticancer therapeutic methodologies. Immune evasions, metabolic modifications, imperfect apoptotic component, modification in upstream or downstream RAS signaling, altered nuclear factor kappa B actions, imbalanced autophagy design and distortedly controlled angiogenesis are distinguishing features of cancer.

Methods: On the basis of systemic research and analysis of the current online available database, we analyzed and reported about the key signaling pathway engaged with cancer development outlining the effectiveness of different therapeutic measures and targets that have been created or are being researched to obstruct the cancer development.

Results: A number of signaling pathways, for example, resistant, metabolism, apoptosis, RAS protein, nuclear factor kappa B, autophagy, and angiogenesis have been perceived as targets for drug treatment to control the advancement, development and administration of cancer.

Conclusion: A noteworthy challenge for future medication advancement is to detail a synthesis treatment influencing distinctive targets to enhance the treatment of cancer.

Keywords: Cancer management, key signaling pathways, therapeutic approaches, autophagy, RAS protein, homeostatic controls.

Graphical Abstract

[1]
Sever R, Brugge JS. Signal transduction in cancer. Cold Spring Harbor Perspect Med 2015; 5(4) a006098
[2]
Vinay DS, Ryan EP, Pawelec G, et al. Immune evasion in cancer: Mechanistic basis and therapeutic strategies. Semin Cancer Biol 2015; 35: S185-s98.
[3]
Lin Y, Bai L, Chen W, Xu S. The NF-kappaB activation pathways, emerging molecular targets for cancer prevention and therapy. Expert Opin Therapeut Targets 2010; 14(1): 45-55.
[4]
Hassan M, Watari H, AbuAlmaaty A, Ohba Y, Sakuragi N. Apoptosis and molecular targeting therapy in cancer. BioMed Res Int 2014; 2014 150845
[5]
Nagelkerke A, Bussink J, Geurts-Moespot A, Sweep FC, Span PN. Therapeutic targeting of autophagy in cancer. Part II: Pharmacological modulation of treatment-induced autophagy. Semin Cancer Biol 2015; 31: 99-105.
[6]
Galluzzi L, Kepp O, Heiden MGV, Kroemer G. Metabolic targets for cancer therapy. Nat Rev Drug Discov 2013; 12(11): 829-46.
[7]
Bahrami A, Hassanian SM. ShahidSales S, et al. Targeting RAS signaling pathway as a potential therapeutic target in the treatment of colorectal cancer. J Cell Physiol 2018; 233(3): 2058-66.
[8]
Zhao Y, Adjei AA. Targeting angiogenesis in cancer therapy: Moving beyond vascular endothelial growth factor. Oncologist 2015; 20(6): 660-73.
[9]
Thorsson V, Gibbs DL, Brown SD, et al. The immune landscape of cancer. Immunity 2018; 48(4): 812-30.
[10]
Andersen MH. The specific targeting of immune regulation: T-cell responses against Indoleamine 2,3-dioxygenase. Cancer Immunol Immunother 2012; 61(8): 1289-97.
[11]
Byrne WL, Mills KH, Lederer JA, O’Sullivan GC. Targeting regulatory T cells in cancer. Cancer Res 2011; 71(22): 6915-20.
[12]
Kim YS, Kim YJ, Lee JM, et al. Functional changes in myeloidderived suppressor cells (MDSCs) during tumor growth: FKBP51 contributes to the regulation of the immunosuppressive function of MDSCs. J Immunol (Baltimore, Md : 1950) 2012; 188(9): 4226-34.
[13]
Singh S, Mehta N, Lilan J, Budhthoki MB, Chao F, Yong L. Initiative action of tumor-associated macrophage during tumor metastasis. Biochim Open 2017; 4: 8-18.
[14]
Hu P, Liu Q, Deng G, et al. The prognostic value of cytotoxic T-lymphocyte antigen 4 in cancers: A systematic review and meta-analysis. Sci Reports 2017; 7: 42913.
[15]
Vinay DS, Kwon BS. Immunotherapy of cancer with 4-1BB. Mol Cancer Ther 2012; 11(5): 1062-70.
[16]
Topalian SL, Drake CG, Pardoll DM. Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity. Curr Opin Immunol 2012; 24(2): 207-12.
[17]
Du W, Yang M, Turner A, et al. TIM-3 as a Target for cancer immunotherapy and mechanisms of action. Int J Mol Sci 2017; 18(3): 645.
[18]
Shashidharamurthy R, Bozeman EN, Patel J, Kaur R, Meganathan J, Selvaraj P. Immunotherapeutic strategies for cancer treatment: A novel protein transfer approach for cancer vaccine development. Med Res Rev 2012; 32(6): 1197-219.
[19]
Zhu F, Liang Y, Chen D, Li Y. Melanoma antigen gene family in the cancer immunotherapy. Cancer Transl Med 2016; 2(3): 85.
[20]
Gjerstorff MF, Andersen MH, Ditzel HJ. Oncogenic cancer/testis antigens: Prime candidates for immunotherapy. Oncotarget 2015; 6(18): 15772.
[21]
Li J, Zou X, Li C, et al. Expression of novel cancer/testis antigen TMEM31 increases during metastatic melanoma progression. Oncol Lett 2017; 13(4): 2269-73.
[22]
Leão R, Apolónio JD, Lee D, Figueiredo A, Tabori U, Castelo-Branco P. Mechanisms of human telomerase reverse transcriptase (h TERT) regulation: Clinical impacts in cancer. J Biomed Sci 2018; 25(1): 22.
[23]
Shepelev MV, Kopantzev EP, Vinogradova TV, Sverdlov ED, Korobko IV. hTERT and BIRC5 gene promoters for cancer gene therapy: A comparative study. Oncol Lett 2016; 12(2): 1204-10.
[24]
Rama AR, Aguilera A, Melguizo C, Caba O, Prados J. Tissue specific promoters in colorectal cancer. Dis Markers 2015; 2015390161
[25]
Qi XW, Zhang F, Wu H, et al. Wilms’ tumor 1 (WT1) expression and prognosis in solid cancer patients: A systematic review and meta-analysis. Sci Rep 2015; 5: 8924.
[26]
Maki T, Ikeda H, Kuroda A, et al. Differential detection of cytoplasmic Wilms tumor 1 expression by immunohistochemistry, western blotting and mRNA quantification. Int J Oncol 2017; 50(1): 129-40.
[27]
Vinay DS, Ryan EP, Pawelec G, et al. Immune evasion in cancer: Mechanistic basis and therapeutic strategies. In: Seminars in cancer biology. Academic Press: USA 2015.
[28]
Ebstein F, Keller M, Paschen A, et al. Exposure to Melan-A/MART-1 26-35 tumor epitope specific CD8+ T cells reveals immune escape by affecting the ubiquitin-proteasome system (UPS). Sci Reports 2016; 6: 25208.
[29]
Faure F, Jouve M, Lebhar‐Peguillet I, et al. Blood monocytes sample M elanA/MART 1 antigen for long‐lasting cross‐presentation to CD 8+ T cells after differentiation into dendritic cells. Int J Cancer 2018; 142(1): 133-44.
[30]
Liu MA. DNA vaccines: An historical perspective and view to the future. Immunol Rev 2011; 239(1): 62-84.
[31]
Vander Heiden MG, Lunt SY, Dayton TL, et al. Metabolic pathway alterations that support cell proliferation. In: Cold Spring Harbor symposia on quantitative biology. Cold Spring Harbor Laboratory Press: NY, USA 2011.
[32]
Gupta S, Roy A, Dwarakanath BS. Metabolic cooperation and competition in the tumor microenvironment: Implications for therapy. Front Oncol 2017; 7: 68.
[33]
Shi L, Pan H, Liu Z, Xie J, Han W. Roles of PFKFB3 in cancer. Signal Transduct Target Ther 2017; 2: 17044.
[34]
Birsoy K, Wang T, Possemato R, et al. MCT1-mediated transport of a toxic molecule is an effective strategy for targeting glycolytic tumors. Nat Genet 2013; 45(1): 104-8.
[35]
Dong G, Mao Q, Xia W, et al. PKM2 and cancer: The function of PKM2 beyond glycolysis. Oncol Lett 2016; 11(3): 1980-6.
[36]
Shoshan MC. 3-bromopyruvate: Targets and outcomes. J Bioenerg Biomembr 2012; 44(1): 7-15.
[37]
Gautier EL, Westerterp M, Bhagwat N, et al. HDL and Glut1 inhibition reverse a hypermetabolic state in mouse models of myeloproliferative disorders. J Exper Med 2013; 210(2): 339-53.
[38]
Zhan T, Digel M, Kuch EM, Stremmel W, Fullekrug J. Silybin and dehydrosilybin decrease glucose uptake by inhibiting GLUT proteins. J Cell Biochem 2011; 112(3): 849-59.
[39]
Lee JY, Lee I, Chang WJ, et al. MCT4 as a potential therapeutic target for metastatic gastric cancer with peritoneal carcinomatosis. Oncotarget 2016; 7(28): 43492.
[40]
Le A, Cooper CR, Gouw AM, et al. Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression. Proc Nat Acad Sci USA 2010; 107(5): 2037-42.
[41]
Yuan W, Wu S, Guo J, et al. Silencing of TKTL1 by siRNA inhibits proliferation of human gastric cancer cells in vitro and in vivo. Cancer Biol Ther 2010; 9(9): 710-6.
[42]
Hitosugi T, Zhou L, Elf S, et al. Phosphoglycerate mutase 1 coordinates glycolysis and biosynthesis to promote tumor growth. Cancer Cell 2012; 22(5): 585-600.
[43]
Possemato R, Marks KM, Shaul YD, et al. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature 2011; 476(7360): 346-50.
[44]
Shuvalov O, Petukhov A, Daks A, Fedorova O, Vasileva E, Barlev NA. One-carbon metabolism and nucleotide biosynthesis as attractive targets for anticancer therapy. Oncotarget 2017; 8(14): 23955.
[45]
Pistritto G, Trisciuoglio D, Ceci C, Garufi A, D’Orazi G. Apoptosis as anticancer mechanism: Function and dysfunction of its modulators and targeted therapeutic strategies. Aging (Albany NY) 2016; 8(4): 603.
[46]
Hassan M, Watari H, AbuAlmaaty A, Ohba Y, Sakuragi N. Apoptosis and molecular targeting therapy in cancer. BioMed Res Int 2014; 2014 150845
[47]
Shao Y, Le K, Cheng H, Aplin AE. NF-κB regulation of c-FLIP promotes TNFα-mediated RAF inhibitor resistance in melanoma. J Invest Dermatol 2015; 135(7): 1839-48.
[48]
Baig S, Seevasant I, Mohamad J, Mukheem A, Huri HZ, Kamarul T. Potential of apoptotic pathway-targeted cancer therapeutic research: Where do we stand? Cell Death Dis 2017; 7(1)e2058
[49]
Um HD. Bcl-2 family proteins as regulators of cancer cell invasion and metastasis: A review focusing on mitochondrial respiration and reactive oxygen species. Oncotarget 2016; 7(5): 5193.
[50]
de Almagro MC, Vucic D. The inhibitor of apoptosis (IAP) proteins are critical regulators of signaling pathways and targets for anti-cancer therapy. Exper Oncol 2012; 34(3): 200-11.
[51]
Hsu TS, Mo ST, Hsu PN, Lai MZ. c-FLIP is a target of the E3 ligase deltex1 in gastric cancer. Cell Death Dis 2018; 9(2): 135.
[52]
Green DR, Evan GI. A matter of life and death. Cancer Cell 2002; 1(1): 19-30.
[53]
Damaskos C, Valsami S, Kontos M, et al. Histone deacetylase inhibitors: an attractive therapeutic strategy against breast cancer. Anticancer Res 2017; 37(1): 35-46.
[54]
Tzifi F, Economopoulou C, Gourgiotis D, Ardavanis A, Papageorgiou S, Scorilas A. The role of BCL2 family of apoptosis regulator proteins in acute and chronic leukemias. Adv Hematol 2012; 2012 524308
[55]
Fulda S, Debatin KM. Caspase activation in cancer therapy Landes Bioscience; Austin: TX. 2000-2013.
[56]
Rooswinkel RW, van de Kooij B, de Vries E, et al. Anti-apoptotic potency of Bcl-2 proteins primarily relies on their stability, not binding selectivity. Blood 2014; 123(18): 2806-15.
[57]
Yuan C, Liu X, Liu X, et al. The GADD45A (1506T> C) polymorphism is associated with ovarian cancer susceptibility and prognosis. PloS One 2015; 10(9) e0138692
[58]
Graupner V, Alexander E, Overkamp T, et al. Differential regulation of the proapoptotic multidomain protein Bak by p53 and p73 at the promoter level. Cell Death Differ 2011; 18(7): 1130.
[59]
Akpinar B, Bracht EV, Reijnders D, et al. 5-Fluorouracil-induced RNA stress engages a TRAIL-DISC-dependent apoptosis axis facilitated by p53. Oncotarget 2015; 6(41): 43679.
[60]
Dasari S, Tchounwou PB. Cisplatin in cancer therapy: Molecular mechanisms of action. Eur J Pharmacol 2014; 740: 364-78.
[61]
Weaver BA. How Taxol/paclitaxel kills cancer cells. Mol Biol Cell 2014; 25(18): 2677-81.
[62]
Rivankar S. An overview of doxorubicin formulations in cancer therapy. J Cancer Res Therapeut 2014; 10(4): 853.
[63]
Fotopoulou C. Limitations to the use of carboplatin-based therapy in advanced ovarian cancer. Eur J Cancer, Suppl 2014; 12(2): 13-6.
[64]
Rajasekharan S, Raman T. Ras and Ras mutations in cancer. Open Life Sci 2013; 8(7): 609-24.
[65]
Stanley RJ, Thomas GM. Activation of G proteins by guanine nucleotide exchange factors relies on GTPase activity. PloS One 2016; 11(3) e0151861
[66]
Prior IA, Lewis PD, Mattos C. A comprehensive survey of Ras mutations in cancer. Cancer Res 2012; 72(10): 2457-67.
[67]
Huang O, Wu D, Xie F, et al. Targeting rho guanine nucleotide exchange factor ARHGEF5/TIM with auto-inhibitory peptides in human breast cancer. Amino Acids 2015; 47(6): 1239-46.
[68]
Ahmed Z, Timsah Z, Suen KM, et al. Grb2 monomer–dimer equilibrium determines normal versus oncogenic function. Nat Commun 2015; 6: 7354.
[69]
Niemitz E. Ras pathway activation in breast cancer. Nat Genet 2013; 45(11): 1273.
[70]
Levy-Apter E, Finkelshtein E, Vemulapalli V, Li SS, Bedford MT, Elson A. Adaptor protein GRB2 promotes Src tyrosine kinase activation and podosomal organization by protein-tyrosine phosphatase ϵ in osteoclasts. J Biol Chem 2014; 289(52): 36048-58.
[71]
Lee KH, Koh M, Moon A. Farnesyl transferase inhibitor FTI-277 inhibits breast cell invasion and migration by blocking H-Ras activation. Oncol Lett 2016; 12(3): 2222-6.
[72]
Aramini JM, Vorobiev SM, Tuberty LM, et al. The RAS-binding domain of human BRAF protein serine/threonine kinase exhibits allosteric conformational changes upon binding HRAS. Structure 2015; 23(8): 1382-93.
[73]
Cseh B, Doma E, Baccarini M. “RAF” neighborhood: Protein–protein interaction in the Raf/Mek/Erk pathway. FEBS Lett 2014; 588(15): 2398-406.
[74]
Rauch J, Volinsky N, Romano D, Kolch W. The secret life of kinases: functions beyond catalysis. Cell Commun Signal 2011; 9(1): 23.
[75]
Manning BD, Toker A. AKT/PKB signaling: Navigating the network. Cell 2017; 169(3): 381-405.
[76]
Xue G, Zippelius A, Wicki A, et al. Integrated Akt/PKB signaling in immunomodulation and its potential role in cancer immunotherapy. J Nat Cancer Inst 2015; 107(7) djv171
[77]
Liu T, Zhang L, Joo D, Sun SC. NF-κB signaling in inflammation. Signal Transduct Target Ther 2017; 2: 17023.
[78]
Park MH, Hong JT. Roles of NF-κB in cancer and inflammatory diseases and their therapeutic approaches. Cells 2016; 5(2): 15.
[79]
Xia Y, Shen S, Verma IM. NF-κB, an active player in human cancers. Cancer Immunol Res 2014; 2(9): 823-30.
[80]
Yan M, Schwaederle M, Arguello D, Millis SZ, Gatalica Z, Kurzrock R. HER2 expression status in diverse cancers: Review of results from 37,992 patients. Cancer Metast Rev 2015; 34(1): 157-64.
[81]
Piacentini M, D’Eletto M, Farrace MG, et al. Characterization of distinct sub-cellular location of transglutaminase type II: Changes in intracellular distribution in physiological and pathological states. Cell Tissue Res 2014; 358(3): 793-805.
[82]
Ghezeldasht SA, Shirdel A, Assarehzadegan MA, et al. Human T lymphotropic virus type I (HTLV-I) oncogenesis: Molecular aspects of virus and host interactions in pathogenesis of adult T cell leukemia/lymphoma (ATL). Iran J Basic Med Sci 2013; 16(3): 179.
[83]
Liu D, Cui L, Hao R, Wang Y, He J, Guo D. Hepatitis B virus polymerase suppresses NF-κB signaling by inhibiting the activity of IKKs via interaction with Hsp90β. PLoS One 2014; 9(3)e91658
[84]
Hoesel B, Schmid JA. The complexity of NF-κB signaling in inflammation and cancer. Mol Cancer 2013; 12(1): 86.
[85]
Landskron G, De la Fuente M, Thuwajit P, Thuwajit C, Hermoso MA. Chronic inflammation and cytokines in the tumor microenvironment. J Immunol Res 2014; 2014149185
[86]
Ba Q, Li J, Huang C, et al. Effects of benzo [a] pyrene exposure on human hepatocellular carcinoma cell angiogenesis, metastasis, and NF-κB signaling. Environ Health Perspect 2015; 123(3): 246.
[87]
Strickson S, Campbell DG, Emmerich CH, et al. The anti-inflammatory drug BAY 11-7082 suppresses the MyD88-dependent signalling network by targeting the ubiquitin system. Biochem J 2013; 451(3): 427-37.
[88]
Dou A, Wang Z, Zhao J, Liu J, Zheng C. Identification of therapeutic target genes with DNA microarray in multiple myeloma cell line treated by IKKβ/NF-κB inhibitor. Acta Cirurg Brasil 2014; 29(11): 696-702.
[89]
Wu L, Shao L, Li M, et al. BMS-345541 sensitizes MCF-7 breast cancer cells to ionizing radiation by selective inhibition of homologous recombinational repair of DNA double-strand breaks. Radiat Res 2012; 179(2): 160-70.
[90]
Liu Q, Wu H, Chim SM, et al. SC-514, a selective inhibitor of IKKβ attenuates RANKL-induced osteoclastogenesis and NF-κB activation. Biochem Pharmacol 2013; 86(12): 1775-83.
[91]
von Heideman A, Berglund Å, Larsson R, Nygren P. Safety and efficacy of NAD depleting cancer drugs: Results of a phase I clinical trial of CHS 828 and overview of published data. Cancer Chemother Pharmacol 2010; 65(6): 1165-72.
[92]
Liu S, Chen Z, Zhu F, Hu Y. IκB kinase alpha and cancer. J Interferon Cytokine Res 2012; 32(4): 152-8.
[93]
Kubiczkova L, Pour L, Sedlarikova L, Hajek R, Sevcikova S. Proteasome inhibitors–molecular basis and current perspectives in multiple myeloma. J Cell Mol Med 2014; 18(6): 947-61.
[94]
Chen D, Frezza M, Schmitt S, Kanwar J, Dou QP. Bortezomib as the first proteasome inhibitor anticancer drug: current status and future perspectives. Curr Cancer Drug Targets 2011; 11(3): 239-53.
[95]
Bianchini G, Gianni L. The immune system and response to HER2-targeted treatment in breast cancer. Lancet Oncol 2014; 15(2): e58-68.
[96]
Troiani T, Napolitano S, Della Corte CM, et al. Therapeutic value of EGFR inhibition in CRC and NSCLC: 15 years of clinical evidence. ESMO Open 2016; 1(5) e000088
[97]
Wang Y, Schmid-Bindert G, Zhou C. Erlotinib in the treatment of advanced non-small cell lung cancer: An update for clinicians. Therapeut Adv Med Oncol 2012; 4(1): 19-29.
[98]
Seront E, Boidot R, Bouzin C, et al. Tumour hypoxia determines the potential of combining mTOR and autophagy inhibitors to treat mammary tumours. Brit J Cancer 2013; 109(10): 2597-606.
[99]
Maycotte P, Thorburn A. Autophagy and cancer therapy. Cancer Biol Ther 2011; 11(2): 127-37.
[100]
Arruebo M, Vilaboa N, Sáez-Gutierrez B, et al. Assessment of the evolution of cancer treatment therapies. Cancers 2011; 3(3): 3279-330.
[101]
Chaachouay H, Ohneseit P, Toulany M, Kehlbach R, Multhoff G, Rodemann HP. Autophagy contributes to resistance of tumor cells to ionizing radiation. Radiother Oncol 2011; 99(3): 287-92.
[102]
Cufi S, Vazquez-Martin A, Oliveras-Ferraros C, et al. The anti-malarial chloroquine overcomes primary resistance and restores sensitivity to trastuzumab in HER2-positive breast cancer. Sci Reports 2013; 3: 2469.
[103]
Sui X, Kong N, Ye L, et al. p38 and JNK MAPK pathways control the balance of apoptosis and autophagy in response to chemotherapeutic agents. Cancer Lett 2014; 344(2): 174-9.
[104]
Li X, Fan Z. The epidermal growth factor receptor antibody cetuximab induces autophagy in cancer cells by downregulating HIF-1alpha and Bcl-2 and activating the beclin 1/hVps34 complex. Cancer Res 2010; 70(14): 5942-52.
[105]
Li X, Lu Y, Pan T, Fan Z. Roles of autophagy in cetuximab-mediated cancer therapy against EGFR. Autophagy 2010; 6(8): 1066-77.
[106]
Fulda S. Autophagy in cancer therapy. Front Oncol 2017; 7: 128.
[107]
Marinković M, Šprung M, Buljubašić M, Novak I. Autophagy modulation in cancer: Current knowledge on action and therapy. Oxidat Med Cell Longev 2018; 2018 8023821
[108]
Kuwahara Y, Oikawa T, Ochiai Y, et al. Enhancement of autophagy is a potential modality for tumors refractory to radiotherapy. Cell Death Dis 2011; 2 e177
[109]
Lai Y, Yu X, Lin X, He S. Inhibition of mTOR sensitizes breast cancer stem cells to radiation-induced repression of self-renewal through the regulation of MnSOD and Akt. Int J Mol Med 2016; 37(2): 369-77.
[110]
Nassim R, Mansure JJ, Chevalier S, Cury F, Kassouf W. Combining mTOR inhibition with radiation improves antitumor activity in bladder cancer cells in vitro and in vivo: A novel strategy for treatment. PloS One 2013; 8(6) e65257
[111]
Nam HY, Han MW, Chang HW, et al. Radioresistant cancer cells can be conditioned to enter senescence by mTOR inhibition. Cancer Res 2013; 73(14): 4267-77.
[112]
Memmott RM, Mercado JR, Maier CR, Kawabata S, Fox SD, Dennis PA. Metformin prevents tobacco carcinogen--induced lung tumorigenesis. Cancer Prevent Res 2010; 3(9): 1066-76.
[113]
Mizushima N, Yoshimori T, Levine B. Methods in mammalian autophagy research. Cell 2010; 140(3): 313-26.
[114]
Jones SA, Mills KH, Harris J. Autophagy and inflammatory diseases. Immunol Cell Biol 2013; 91(3): 250-8.
[115]
Xie R, Nguyen S, McKeehan WL, Liu L. Acetylated microtubules are required for fusion of autophagosomes with lysosomes. BMC Cell Biol 2010; 11(1): 89.
[116]
Jiang PD, Zhao YL, Deng XQ, et al. Antitumor and antimetastatic activities of chloroquine diphosphate in a murine model of breast cancer. Biomed Pharmacother 2010; 64(9): 609-14.
[117]
Ray A, Vasudevan S, Sengupta S. 6-Shogaol inhibits breast cancer cells and stem cell-like spheroids by modulation of Notch signaling pathway and induction of autophagic cell death. PLoS One 2015; 10(9) e0137614
[118]
Gallagher LE, Radhi OA, Abdullah MO, McCluskey AG, Boyd M, Chan EY. Lysosomotropism depends on glucose: A chloroquine resistance mechanism. Cell Death Dis 2017; 8(8)e3014
[119]
Bielenberg DR, Zetter BR. The contribution of angiogenesis to the process of metastasis. Cancer J (Sudbury, Mass) 2015; 21(4): 267.
[120]
Chien MH, Lee LM, Hsiao M, et al. Inhibition of metastatic potential in breast carcinoma in vivo and in vitro through targeting VEGFRs and FGFRs. Evid Based Complement Alternat Med 2013; 2013 718380
[121]
Chekhonin VP, Shein SA, Korchagina AA, Gurina OI. VEGF in tumor progression and targeted therapy. Curr Cancer Drug Targets 2013; 13(4): 423-43.
[122]
Goel HL, Mercurio AM. VEGF targets the tumour cell. Nat Rev Cancer 2013; 13(12): 871.
[123]
Stacker SA, Achen MG. The VEGF signaling pathway in cancer: The road ahead. Chinese J Cancer 2013; 32(6): 297.
[124]
Kieran MW, Kalluri R, Cho YJ. The VEGF pathway in cancer and disease: responses, resistance, and the path forward. Cold Spring Harbor Perspect Med 2012; 2(12)a006593
[125]
Abhinand CS, Raju R, Soumya SJ, Arya PS, Sudhakaran PR. VEGF-A/VEGFR2 signaling network in endothelial cells relevant to angiogenesis. J Cell Commun Signal 2016; 10(4): 347-54.
[126]
Ferrara N. Pathways mediating VEGF-independent tumor angiogenesis. Cytokine Growth Factor Rev 2010; 21(1): 21-6.
[127]
Heldin CH. Targeting the PDGF signaling pathway in tumor treatment. Cell Commun Signal 2013; 11: 97.
[128]
Hallinan N, Finn S, Cuffe S, Rafee S, O’Byrne K, Gately K. Targeting the fibroblast growth factor receptor family in cancer. Cancer Treat Rev 2016; 46: 51-62.
[129]
André F, Cortés J. Rationale for targeting fibroblast growth factor receptor signaling in breast cancer. Breast Cancer Res Treat 2015; 150(1): 1-8.
[130]
Graveel CR, Tolbert D, Vande Woude GF. MET: A critical player in tumorigenesis and therapeutic target. Cold Spring Harb perspect Biol 2013; 5(7)a009209
[131]
Xiang C, Chen J, Fu P. HGF/Met signaling in cancer invasion: the impact on cytoskeleton remodeling. Cancers 2017; 9(5): 44.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy