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Cancer Biomarkers: Status and Its Future Direction

  • Review Article
  • Published:
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Abstract

Biomarkers are helpful for disease diagnosis, monitoring disease progression, predicting disease recurrence, treatment monitoring, and efficacy, especially in the domain of cancer management and therapeutics. Clinical cancer biomarker utilization is progressively increasing with increase in and better access to healthcare by the growing populations worldwide. Early cancer detection and therapeutics enhancement remain at the core to increase our cancer management and control abilities. A biomarker can help detect cancer at an early stage as well as aid the clinicians in individualization of therapeutics enhancing the clinical efficacy of cancer therapy. Over the years, several biomarkers have been established and are in regular use. Nonetheless, discovering new cancer biomarkers, which are more sensitive, specific, and clinically convenient, remains important. The current review critically analyzes the existing and established cancer biomarkers as well as futuristic biomarkers for clinicians, surgeons, oncologists, and researchers. A tabular summary at the end of the article and compilation of up to date literature in the domain should be useful ready reckoners for clinicians, oncologists, and researchers alike.

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Abbreviations

ACT :

Average cancer therapy

AFP :

Alpha-fetoprotein

ARPA :

ADP-ribose polymer adduct

BRCA :

Breast cancer–associated genes

CA 125 :

Cancer antigen 125

CA 15-3 :

Cancer antigen 15–3

CA 19-9 :

Cancer antigen 19–9 or carbohydrate antigen 19–9

CA27-29 :

Cancer antigen 27–29

CBs :

Cancer biomarkers

CCBs :

Clinical cancer biomarkers

CDKN1A :

Cyclin-dependent kinase inhibitor 1A

CEA :

Carcinoembryonic antigen

CT :

Cancer therapy or cancer therapeutics

ECBs :

Experimental cancer biomarkers

hCG :

Human chorionic gonadotrophin

HE4 :

Human epididymis protein 4

HER2 :

Human epidermal growth factor receptor 2

HSP :

Heat-shock protein

MIA :

Multivariate index assay

mTOR :

Mammalian target of rapamycin

NFIC :

Nuclear factor 1-C

OVA :

Ovarian Malignancy Algorithm

PPCT :

Personalized and precise cancer therapy

PSA :

Prostate-specific antigen

ROMA :

Risk of Ovarian Malignancy Algorithm

Tg :

Thyroglobulin

VEGF :

Vascular endothelial growth factor

References

  1. Lassere MN (2008) The Biomarker-Surrogacy Evaluation Schema: a review of the biomarker-surrogate literature and a proposal for a criterion-based, quantitative, multidimensional hierarchical levels of evidence schema for evaluating the status of biomarkers as surrogate endpoints. Stat Methods Med Res 17:303–340

    Article  PubMed  Google Scholar 

  2. World Health Organization & International Programme on Chemical Safety (1993) Biomarkers and risk assessment: concepts and principles / published under the joint sponsorship of the United Nations environment Programme, the International Labour Organisation, and the World Health Organization. WHO https://apps.who.int/iris/handle/10665/39037

  3. Henry NL, Hayes DF (2012) Cancer biomarkers. Mol Oncol 6:140–146

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Simon R, Roychowdhury S (2013) Implementing personalized cancer genomics in clinical trials. Nat Rev Drug Discov 12:358–369

    Article  PubMed  CAS  Google Scholar 

  5. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, Gianni L, Baselga J, Bell R, Jackisch C, Cameron D (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353:1659–1672

    Article  PubMed  CAS  Google Scholar 

  6. Van Cutsem E, Köhne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, D’Haens G, Pintér T, Lim R, Bodoky G, Roh JK (2009) Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 360:1408–1417

    Article  PubMed  Google Scholar 

  7. Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, Baehner FL, Walker MG, Watson D, Park T, Hiller W (2004) A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 351:2817–2826

    Article  PubMed  CAS  Google Scholar 

  8. Coleman RL, Herzog TJ, Chan DW, Munroe DG, Pappas TC, Smith A, Zhang Z, Wolf J (2016) Validation of a second-generation multivariate index assay for malignancy risk of adnexal masses. Am J Obstet Gynecol 215:82–93

    Article  Google Scholar 

  9. U. S. Food & Drug Administration (2021) List of qualified biomarkers. F D A https://www.fda.gov/drugs/biomarker-qualification-program/list-qualified-biomarkers

  10. James EK (2020) Carcinogenesis. An introduction to interdisciplinary toxicology. Handbook of toxicology pathology (second edition). Academic Press, p 97–110. https://doi.org/10.1016/B978-0-12-813602-7.00008-9

  11. Handy DE, Castro R, Loscalzo J (2011) Epigenetic modifications: basic mechanisms and role in cardiovascular disease. Circulation 123:2145–2156

    Article  PubMed  PubMed Central  Google Scholar 

  12. Collins FS, Varmus H (2015) A new initiative on precision medicine. N Engl J Med 372:793–805

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Nora MAA, Connor T, Ishwarlal J (2021) Genetics, epigenetic mechanism. StatPearls

  14. World Health Organization (2022) Cancer fact sheet. WHO, Geneva. http://www.who.int/health-topics/cancer#tab=tab_1/. Accessed in Feb 2023

  15. Kirwan A, Utratna M, O’Dwyer ME, Joshi L, Kilcoyne M (2015) Glycosylation-based serum biomarkers for cancer diagnostics and prognostics. Biomed Res Int. https://doi.org/10.1155/2015/490531

    Article  PubMed  PubMed Central  Google Scholar 

  16. Crandall BF, Lau HL (1981) Alpha-fetoprotein: a review. Crit Rev Clin Lab Sci 15:127–185

    Article  PubMed  CAS  Google Scholar 

  17. Mizejewski GJ (2018) Alpha-Fetoprotein (AFP) and gastric cancer: why is lethality more prevalent in AFP-secreting than non-secreting tumors? Cancer Ther Oncol Int J. https://doi.org/10.19080/CTOIJ.2018.09.555753

    Article  Google Scholar 

  18. AlSalloom AAM (2016) An update of biochemical markers of hepatocellular carcinoma. Int J Health Sci 10:121–136

    Google Scholar 

  19. Asahina Y, Tsuchiya K, Nishimura T, Muraoka M, Suzuki Y, Tamaki N, Yasui Y, Hosokawa T, Ueda K, Nakanishi H, Itakura J (2013) α-fetoprotein levels after interferon therapy and risk of hepatocarcinogenesis in chronic hepatitis C. Hepatol 58:1253–1262

    Article  CAS  Google Scholar 

  20. Albrecht H, Carraway KL (2011) MUC1 and MUC4: switching the emphasis from large to small. Cancer Biother Radiopharm 26:261–271

    PubMed  PubMed Central  CAS  Google Scholar 

  21. Mukhopadhyay P, Chakraborty S, Ponnusamy MP, Lakshmanan I, Jain M, Batra SK (2011) Mucins in the pathogenesis of breast cancer: implications in diagnosis, prognosis and therapy. Biochim Biophys Acta 1815:224–240

    PubMed  PubMed Central  CAS  Google Scholar 

  22. Mudduwa LK, Wijayaratne GB, Peiris HH, Gunasekera SN, Abeysiriwardhana D, Liyanage N (2018) Elevated pre-surgical CA15-3: does it predict the short-term disease-free survival of breast cancer patients without distant metastasis? Int J Women Health 10:329–335

    Article  CAS  Google Scholar 

  23. Duffy MJ, Evoy D, McDermott EW (2010) CA 15–3: uses and limitation as a biomarker for breast cancer. Clin Chim Acta 411:1869–1874

    Article  PubMed  CAS  Google Scholar 

  24. Perkins GL, Slater ED, Sanders GK, Prichard JG (2003) Serum tumor markers. Am Fam Physician 68:1075–1082

    PubMed  Google Scholar 

  25. Koprowski H, Steplewski Z, Mitchell K, Herlyn M, Herlyn D, Fuhrer P (1979) Colorectal carcinoma antigens detected by hybridoma antibodies. Somatic Cell Genet 5:957–971

    Article  PubMed  CAS  Google Scholar 

  26. Pall M, Iqbal J, Singh SK, Rana SV (2012) CA 19–9 as a serum marker in urothelial carcinoma. Urol Ann 4:98–101

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Kim S, Park BK, Seo JH, Choi J, Choi JW, Lee CK, Chung JB, Park Y, Kim DW (2020) Carbohydrate antigen 19–9 elevation without evidence of malignant or pancreatobiliary diseases. Sci Rep 10:1–9

    Google Scholar 

  28. Ballehaninna UK, Chamberlain RS (2012) The clinical utility of serum CA 19–9 in the diagnosis, prognosis and management of pancreatic adenocarcinoma: an evidence based appraisal. J Gastrointest Oncol 3:105–119

    PubMed  PubMed Central  CAS  Google Scholar 

  29. Kabel AM (2017) Tumor markers of breast cancer: new perspectives. J Oncol Sci 3:5–11

    Article  Google Scholar 

  30. Vaidyanathan K, Vasudevan DM (2012) Organ specific tumor markers: what’s new? Indian J Clin Biochem 27:110–120

    Article  PubMed  CAS  Google Scholar 

  31. Nikhil TG, Dolly R, Staros EB (2021) CA 27–29: reference range, interpretation, collection and panels. Medscape https://emedicine.medscape.com/article/2087535-overview

  32. Lin DC, Genzen JR (2018) Concordance analysis of paired cancer antigen (CA) 15–3 and 27.29 testing. Breast Cancer Res Treat 167:269–276

    Article  PubMed  CAS  Google Scholar 

  33. Muinao T, Boruah HP, Pal M (2018) Diagnostic and prognostic biomarkers in ovarian cancer and the potential roles of cancer stem cells - an updated review. Exp Cell Res 362:1–10

    Article  PubMed  CAS  Google Scholar 

  34. Menczer J, Ben-Shem E, Golan A, Levy T (2015) The significance of normal pre-treatment levels of CA125 (< 35 U/mL) in epithelial ovarian carcinoma. Rambam. Maimonides. Med J. https://doi.org/10.5041/RMMJ.10180

  35. Pepin K, Carmen MD, Brown A, Dizon DS (2014) CA 125 and epithelial ovarian cancer: role in screening, diagnosis, and surveillance. Am J Hematol 10:22–29

    Google Scholar 

  36. Rustin GJ, Bast RC, Kelloff GJ, Barrett JC, Carter SK, Nisen PD, Sigman CC, Parkinson DR, Ruddon RW (2004) Use of CA-125 in clinical trial evaluation of new therapeutic drugs for ovarian cancer. Clin Cancer Res 10:3919–3926

    Article  PubMed  CAS  Google Scholar 

  37. Pignata S, Cannella L, Leopardo D, Bruni GS, Facchini G, Pisano C (2011) Follow-up with CA125 after primary therapy of advanced ovarian cancer: in favor of continuing to prescribe CA125 during follow-up. Ann Oncol 22:viii40–viii44

  38. Bast RC Jr (2010) CA 125 and the detection of recurrent ovarian cancer: a reasonably accurate biomarker for a difficult disease. Cancer 116:2850–2853

    Article  PubMed  Google Scholar 

  39. Gold P, Freedman SO (1965) Demonstration of tumor-specific antigens in human colonic carcinomata by immunological tolerance and absorption techniques. J Exp Med 121:439–462

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Zhong W, Yu Z, Zhan J, Yu T, Lin Y, Xia ZS, Yuan YH, Chen QK (2015) Association of serum levels of CEA, CA199, CA125, CYFRA21-1 and CA72-4 and disease characteristics in colorectal cancer. Pathol Oncol Res 21:83–95

    Article  PubMed  CAS  Google Scholar 

  41. Saito G, Sadahiro S, Kamata H, Miyakita H, Okada K, Tanaka A, Suzuki T (2017) Monitoring of serum carcinoembryonic antigen levels after curative resection of colon cancer: cut off values determined according to preoperative levels enhance the diagnostic accuracy for recurrence. Oncology 92:276–282

    Article  PubMed  CAS  Google Scholar 

  42. Xie HL, Gong YZ, Kuang JA, Gao F, Tang SY, Gan JL (2019) The prognostic value of the postoperative serum CEA levels/preoperative serum CEA levels ratio in colorectal cancer patients with high preoperative serum CEA levels. Cancer Manag Res 11:7499–7511

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Sørensen CG, Karlsson WK, Pommergaard HC, Burcharth J, Rosenberg J (2016) The diagnostic accuracy of carcinoembryonic antigen to detect colorectal cancer recurrence–a systematic review. Int J Surg 25:134–144

    Article  PubMed  Google Scholar 

  44. Wang Z, Wang W, Xu S, Wang S, Tu Y, Xiong Y, Mei J, Wang C (2016) The role of MAPK signaling pathway in the Her-2-positive meningiomas. Oncol Rep 36:685–695

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Yan M, Schwaederle M, Arguello D, Millis SZ, Gatalica Z, Kurzrock R (2015) HER2 expression status in diverse cancers: review of results from 37,992 patients. Cancer Metastasis Rev 34:157–164

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Furrer D, Paquet C, Jacob S, Diorio C (2018) The Human Epidermal Growth Factor Receptor 2 (HER2) as a prognostic and predictive biomarker: molecular insights into HER2 activation and diagnostic implications. Cancer Prognosis. https://doi.org/10.5772/intechopen.78271

    Article  Google Scholar 

  47. Wang XY, Zheng ZX, Sun Y, Bai YH, Shi YF, Zhou LX, Yao YF, Wu AW, Cao DF (2019) Significance of HER2 protein expression and HER2 gene amplification in colorectal adenocarcinomas. World J Gastrointest Oncol 11:335–347

    Article  PubMed  PubMed Central  Google Scholar 

  48. Ferraro S, Panteghini M (2019) Making new biomarkers a reality: the case of serum human epididymis protein 4. Clin Chem Lab Med 57:1284–1294

    Article  PubMed  CAS  Google Scholar 

  49. Lu R, Sun X, Xiao R, Zhou L, Gao X, Guo L (2012) Human epididymis protein 4 (HE4) plays a key role in ovarian cancer cell adhesion and motility. Biochem Biophys Res Commun 419:274–280

    Article  PubMed  CAS  Google Scholar 

  50. Zhu L, Zhuang H, Wang H, Tan M, Schwab CL, Deng L, Gao J, Hao Y, Li X, Gao S, Liu J (2016) Overexpression of HE4 (human epididymis protein 4) enhances proliferation, invasion and metastasis of ovarian cancer. Oncotarget 7:729–744

    Article  PubMed  Google Scholar 

  51. Moradi A, Srinivasan S, Clements J, Batra J (2019) Beyond the biomarker role: prostate-specific antigen (PSA) in the prostate cancer microenvironment. Cancer Metastasis Rev 38:333–346

    Article  PubMed  CAS  Google Scholar 

  52. Hong SK (2014) Kallikreins as biomarkers for prostate cancer. BioMed Res Int. https://doi.org/10.1155/2014/526341

    Article  PubMed  PubMed Central  Google Scholar 

  53. Siemińska L, Borowski A, Marek B, Nowak M, Kajdaniuk D, Warakomski J, Kos-Kudła B (2018) Serum concentrations of adipokines in men with prostate cancer and benign prostate hyperplasia. Endokrynol Pol 69:120–127

    PubMed  Google Scholar 

  54. Duffy MJ (2020) Biomarkers for prostate cancer: prostate-specific antigen and beyond. Clin Chem Lab Med 58:326–339

    Article  PubMed  CAS  Google Scholar 

  55. Tamhane S, Gharib H (2016) Thyroid nodule update on diagnosis and management. Clin Diabetes Endocrinol 2:1–10

    Google Scholar 

  56. Prpić M, Franceschi M, Romić M, Jukić T, Kusić Z (2018) Thyroglobulin as a tumor marker in differentiated thyroid cancer–clinical considerations. Acta Clin Croat 57:518–526

    PubMed  PubMed Central  Google Scholar 

  57. Hasanbegovic L, Alicelebic S, Sljivo N (2015) Comparison of specific ovarian tumor markers by elecsys analyzer 2010. Acta Inform Med 23:86–89

    Article  PubMed  PubMed Central  Google Scholar 

  58. Ueland FR, Desimone CP, Seamon LG, Miller RA, Goodrich S, Podzielinski I, Sokoll L, Smith A, Van Nagell Jr JR, Zhang Z (2011) Effectiveness of a multivariate index assay in the preoperative assessment of ovarian tumors. Obstet Gynecol 117:1289–1297

    Article  PubMed  Google Scholar 

  59. Zhang Z, Chan DW (2010) The road from discovery to clinical diagnostics: lessons learned from the first FDA-cleared in vitro diagnostic multivariate index assay of proteomic biomarkers. Cancer Epidemiol Biomarkers Prev 19:2995–2999

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Moore RG, McMeekin DS, Brown AK, DiSilvestro P, Miller MC, Allard WJ, Gajewski W, Kurman R, Bast RC Jr, Skates SJ (2009) A novel multiple marker bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in patients with a pelvic mass. Gynecol Oncol 112:40–46

    Article  PubMed  CAS  Google Scholar 

  61. Anton C, Carvalho FM, Oliveira EI, Maciel GA, Baracat EC, Carvalho JP (2012) A comparison of CA125, HE4, risk ovarian malignancy algorithm (ROMA), and risk malignancy index (RMI) for the classification of ovarian masses. Clinics 67:437–441

    Article  PubMed  PubMed Central  Google Scholar 

  62. Wang J, Gao J, Yao H, Wu Z, Wang M, Qi J (2014) Diagnostic accuracy of serum HE4, CA125 and ROMA in patients with ovarian cancer: a meta-analysis. Tumor Biol 35:6127–6138

    Article  CAS  Google Scholar 

  63. Al Musalhi K, Al Kindi M, Al Aisary F, Ramadhan F, Al Rawahi T, Al Hatali K, Mula-Abed WA (2016) Evaluation of HE4, CA-125, risk of ovarian malignancy algorithm (ROMA) and risk of malignancy index (RMI) in the preoperative assessment of patients with adnexal mass. Oman Med J 31:336–344

    Article  PubMed  PubMed Central  Google Scholar 

  64. Sharan RN (2009) 15 poly-ADP-ribosylation in cancer. In: Trygve Tollefsbol (ed) Cancer Epigenetics. CRC Press, Florida, pp 265–279

  65. Chanu TM (2022) PhD thesis entitled Clinical correlation between cancer regression and selected genetic and epigenetic biomarkers in patients undergoing cancer therapy. NEHU, Shillong, India

  66. Sharan RN, Devi BJ, Humtsoe JO, Saikia JR, Kma L (2005) Detection and quantification of poly-ADP-ribosylated cellular proteins of spleen and liver tissues of mice in vivo by slot and Western blot immunoprobing using polyclonal antibody against mouse ADP-ribose polymer. Mol Cell Biochem 278:213–221

    Article  PubMed  CAS  Google Scholar 

  67. Devi BJ, Schneeweiss FHA, Sharan RN (2005) Negative correlation between poly-ADP-ribosylation of spleen cell histone proteins and initial duration of dimethylnitrosamine exposure to mice in vivo measured by Western blot immunoprobe assay: a possible biomarker for cancer detection. Cancer, Detect Prev 29:66–71

    Article  PubMed  CAS  Google Scholar 

  68. Saikia JR, Schneeweiss FHA, Sharan RN (1998) Effects of chronic low-dose arecoline administration on the macromolecular components of bone marrow and spleen cells of mice. Cancer J 11:94–98

    CAS  Google Scholar 

  69. Kma L, Sharan RN (2014) Dimethylnitrosamine induced reduction in the level of poly- ADP ribosylation of histone proteins of blood lymphocytes – a sensitive and reliable biomarker for early detection of cancer. Asia Pac J Cancer Prev 15:6429–6436

    Article  Google Scholar 

  70. Lakadong RO, Kataki AC, Sharan RN (2010) ADP-ribose polymer - a novel and general biomarker of human cancers of head & neck, breast, and cervix. Mol Cancer. https://doi.org/10.1186/1476-4598-9-286

    Article  PubMed  PubMed Central  Google Scholar 

  71. Hoxhaj G, Manning BD (2020) The PI3K–AKT network at the interface of oncogenic signalling and cancer metabolism. Nat Rev Cancer 20:74–88

    Article  PubMed  CAS  Google Scholar 

  72. Degan SE, Gelman IH (2021) Emerging roles for AKT isoform preference in cancer progression pathways. Mol Cancer Res 19:1251–1257

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Turner KM, Sun Y, Ji P, Granberg KJ, Bernard BL, Cogdell DE, Zhou X, Yli-Harja O, Nykter M, Shmulevich I (2015) Genomically amplified Akt3 activates DNA repair pathway and promotes glioma progression. Proc Natl Acad Sci 112:3421–3426

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Gallyas F, Sumegi B, Szabo C (2020) Role of Akt activation in PARP inhibitor resistance in cancer. Cancers 12:532–540

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Guo K, Tang W, Zhuo H, Zhao G (2019) Recent advance of Akt inhibitors in clinical trials. ChemistrySelect 4:9040–9044

    Article  CAS  Google Scholar 

  76. Santana dos Santos E, Lallemand F, Burke L, Stoppa-Lyonnet D, Brown M, Caputo SM, Rouleau E (2018) Non-coding variants in BRCA1 and BRCA2 genes: potential impact on breast and ovarian cancer predisposition. Cancers. https://doi.org/10.3390/cancers10110453

    Article  PubMed  PubMed Central  Google Scholar 

  77. Huang F, Goyal N, Sullivan K, Hanamshet K, Patel M, Mazina OM, Wang CX, An WF, Spoonamore J, Metkar S, Emmitte KA (2016) Targeting BRCA1-and BRCA2-deficient cells with RAD52 small molecule inhibitors. Nucleic Acid Res 44:4189–4199

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Jin TY, Park KS, Nam SE, Yoo YB, Park WS, Yun IJ (2022) BRCA1/2 serves as a biomarker for poor prognosis in breast carcinoma. Intl J Mol Sci 23:3754–3768

    Article  CAS  Google Scholar 

  79. Mazin AV, Zaitseva E, Sung P, Kowalczykowski SC (2000) Tailed duplex DNA is the preferred substrate for Rad51 protein-mediated homologous pairing. EMBO J 19:1148–1156

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  80. Dutto I, Scalera C, Prosperi E (2018) CREBBP and p300 lysine acetyl transferases in the DNA damage response. Cell Mol Life Sci 75:1325–1338

    Article  PubMed  CAS  Google Scholar 

  81. Karimian A, Ahmadi Y, Yousefi B (2016) Multiple functions of p21 in cell cycle, apoptosis and transcriptional regulation after DNA damage. DNA Repair 42:63–71

    Article  PubMed  CAS  Google Scholar 

  82. Bertoli C, Skotheim JM, De Bruin RA (2013) Control of cell cycle transcription during G1 and S phases. Nat Rev Mol Cell Biol 14:518–528

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Abbas T, Dutta A (2009) p21 in cancer: intricate networks and multiple activities. Nat Rev Cancer 9:400–414

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Moor NA, Lavrik OI (2018) Protein–protein interactions in DNA base excision repair. Biochemistry 83:411–422

    PubMed  CAS  Google Scholar 

  85. Weiss RH, Borowsky AD, Seligson D, Lin PY, Dillard-Telm L, Belldegrun AS, Figlin RA, Pantuck AD (2007) p21 is a prognostic marker for renal cell carcinoma: implications for novel therapeutic approaches. J Urol 177:63–69

    Article  PubMed  CAS  Google Scholar 

  86. Nongrum S, Vaiphei ST, Keppen J, Ksoo M, Kashyap E, Sharan RN (2017) Identification and preliminary validation of radiation response proteins(s) in human blood for a high throughput molecular biodosimetry technology for the future. Genome Integr. https://doi.org/10.4103/2041-9414.198910

    Article  PubMed  PubMed Central  Google Scholar 

  87. Das JK, Xiong X, Ren X, Yang JM, Song J (2019) H eat shock proteins in cancer immunotherapy J. Oncol. https://doi.org/10.1155/2019/3267207

    Article  Google Scholar 

  88. Ciocca DR, Calderwood SK (2005) Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones 10:86–103

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  89. Lianos GD, Alexiou GA, Mangano A, Rausei S, Boni L, Dionigi G, Roukos DH (2015) The role of heat shock proteins in cancer. Cancer Lett 360:114–118

    Article  PubMed  CAS  Google Scholar 

  90. Moon A, Bacchini P, Bertoni F, Olvi LG, Santini-Arawo E, Kim YW, Par YK (2010) Expression of heat shock proteins in osteosarcomas. Pathology 42:421–425

    Article  PubMed  CAS  Google Scholar 

  91. Selleck MJ, Senthil M, Wall NR (2017) Making meaningful clinical use of biomarkers. Biomark Insights. https://doi.org/10.1177/1177271917715236

    Article  PubMed  PubMed Central  Google Scholar 

  92. Wang W, Xu X, Tian B, Wang Y, Du L, Sun T, Shi Y, Zhao X, Jing J (2017) The diagnostic value of serum tumor markers CEA, CA19-9, CA125, CA15-3, and TPS in metastatic breast cancer. Clin Chim Acta 470:51–55

    Article  PubMed  CAS  Google Scholar 

  93. Schüler-Toprak S, Treeck O, Ortmann O (2017) Human chorionic gonadotropin and breast cancer. Int J Mol Sci. https://doi.org/10.3390/ijms18071587

    Article  PubMed  PubMed Central  Google Scholar 

  94. Tian T, Li X, Zhang J (2019) mTOR signaling in cancer and mTOR inhibitors in solid tumor targeting therapy. Int J Mol Sci 20:755–764

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  95. Conciatori F, Ciuffreda L, Bazzichetto C, Falcone I, Pilotto S, Bria E, Cognetti F, Milella M (2018) mTOR cross-talk in cancer and potential for combination therapy. Cancers 10:23–34

    Article  PubMed  PubMed Central  Google Scholar 

  96. Zou Z, Tao T, Li H, Zhu X (2020) mTOR signaling pathway and mTOR inhibitors in cancer: Progress and challenges. Cell Biosci 10:1–10

    Article  CAS  Google Scholar 

  97. Lee HK, Lee DS, Park JC (2015) Nuclear factor IC regulates E-cadherin via control of KLF4 in breast cancer. BMC Cancer 15:1–11

    Article  Google Scholar 

  98. Grabowska MM, Elliott AD, DeGraff DJ, Anderson PD, Anumanthan G, Yamashita H, Sun Q, Friedman DB, Hachey DL, Yu X, Sheehan JH (2014) NFI transcription factors interact with FOXA1 to regulate prostate-specific gene expression. Mol Endocrinol 28:949–964

    Article  PubMed  PubMed Central  Google Scholar 

  99. Fane M, Harris L, Smith AG, Piper M (2017) Nuclear factor one transcription factors as epigenetic regulators in cancer. Int J Cancer 140:2634–2641

    Article  PubMed  CAS  Google Scholar 

  100. Yang C, Chng KR (2012) Abstract C2: Nuclear factor I/C collaborates with androgen receptor in transcription regulation in prostate cancer. Cancer Res. https://doi.org/10.1158/1538-7445.PRCA2012-C2

    Article  PubMed  PubMed Central  Google Scholar 

  101. Zenker M, Bunt J, Schanze I, Schanze D, Piper M, Priolo M, Gerkes EH, Gronostajski RM, Richards LJ, Vogt J, Wessels MW (2019) Variants in nuclear factor I genes influence growth and development. Am J Med Gen 181:611–626

    Article  CAS  Google Scholar 

  102. Carmeliet P (2005) VEGF as a key mediator of angiogenesis in cancer. Oncology 69:4–10

    Article  PubMed  CAS  Google Scholar 

  103. Hegde PS, Wallin JJ, Mancao C (2018) Predictive markers of anti-VEGF and emerging role of angiogenesis inhibitors as immunotherapeutics. Semin Cancer Biol 52:117–124

    Article  PubMed  CAS  Google Scholar 

  104. Kulapaditharom B, Boonkitticharoen V, Sritara C (2012) Plasma vascular endothelial growth factor dysregulation in defining aggressiveness of head and neck squamous cell carcinoma. J Oncol 15:12–20

    Google Scholar 

  105. Garcia J, Hurwitz HI, Sandler AB, Miles D, Coleman RL, Deurloo R, Chinot OL (2020) Bevacizumab (Avastin®) in cancer treatment: a review of 15 years of clinical experience and future outlook. Cancer Treat Rev 86:102–117

    Article  Google Scholar 

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Funding

This research was financially supported by grants from (a) International Atomic Energy Agency, Vienna under research contract # 22218 to RNS and (b) DRS-III scheme of the UGC to the Department of Biochemistry. TMC gratefully acknowledges junior and senior research fellowship grants to support her doctoral study under the “Innovation in Science Pursuit for Inspired Research (INSPIRE)” Fellowship scheme of the Government of India.

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Authors and Affiliations

  1. Radiation & Molecular Biology Unit, Department of Biochemistry, North-Eastern Hill University, Shillong, 793022, India

    Tongbram Malemnganbi Chanu & R. N. Sharan

  2. Cancer & Radiation Countermeasures Unit, Depatment of Biochemistry, North-Eastern Hill University, Shillong, 793022, India

    Lakhon Kma

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  1. Tongbram Malemnganbi Chanu
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Correspondence to R. N. Sharan.

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Chanu, T.M., Kma, L. & Sharan, R.N. Cancer Biomarkers: Status and Its Future Direction. Indian J Surg 85, 1323–1335 (2023). https://doi.org/10.1007/s12262-023-03723-1

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