Tumor markers and their diagnostic significance.pptx

An overview of commonly used tumor biomarkers and future direction of research

1. Tumor Markers /Biomarkers Tools for Cancer Screening, Diagnosis and Therapeutics

2. What are tumor markers? Substances produced by tumors or the body’s responses to tumors which provide critical information for screening and early diagnosis prognosis prediction recurrence detection monitoring therapeutic efficacy of various treatment modalities

3. Where are tumor markers found? Tumor tissues or Body fluids such as blood urine stool saliva etc!

4. Characteristics of an ideal tumor marker High sensitivity and specificity Detectable in early stage Elevated levels correlate with tumor burden/stage Decreasing levels indicate treatment response Stable or decrerasing levels indicate disease remission No currently available markers meet these criteria perfectly

5. Classification of Tumor Biomarkers No formal system of classification Classified according to site of origin and type of molecule etc.

6. Classification according to Molecular type/function Hormones - beta HCG, Calcitonin Oncofetal antigens - Alpha fetoprotein, CEA Lineage specific proteins - Immunoglobulins, PSA Mucin and other glycoprotiens - Ca125, Ca19-9 Cell-free DNA - EGFR mutatnts in serum, Tp53 mutants in urine etc.

7. Classification according to tissue of origin /site of detection

8. History of tumor markers

9. Practical applications of tumor markers Screening: Non invasive, cost effective, false + and -ve, PSA, AFP Tumor diagnosis: used as panels, individual markers are not sufficiently sensitive and specific, AFP+cfDNA increases specificity of HCC diagnosis to 94%

10. Practical applications of tumor markers Predicting prognosis and response to therapy: Novel tissue based markers such as her2neu (breast cancer) and PDL-1 (lung cancer) help select patients for targeted therapies Monitoring tumor recurrence/mets: blood based markers, PSA, CEA in hepatic recurrence of gastric cancer, CA19-9 for peritoneal recurrence

11. Brief overview of selected tumor markers

12. Alpha fetoprotein 3–5% CHO-containing glycoprotein AFP gene located in the q arm of chromosome 4 (4q25) Major serum protein in fetal life &till 18 months, falls afterwards Conc in healthy adult serum < 10 μg/L Elevated AFP in ~80% of HCC Used in HCC screening, esp in the global south, also recurrence and metastases (not 100% specific)

13. Carcinoembryonic antigen (CEA) Cell surface glycoprotein, 19q Production in fetal GI tract 9-13 wks Found in normal adult tissues such as the colon, stomach, cervix, sweat glands, and prostate Broad spectrum tumor marker expressed in many tumors 70% of CRC, 55% of pancreatic cancer, 50% of gastric cancer, 45% of lung cancer, 40% of breast cancer, 40% of urethral carcinoma, and 25% of ovarian cancer

14. Carcinoembryonic antigen (CEA) Serum CEA levels are proportional to tumor burden CEA levels provide meaningful prognostic information in breast cancer, CRC (5 yr survival) High levels predict poor outcomes in lung adenocarcinoma patients with mutant EGFRs, and gastric cancer patients with lymph node metastasis Detects tumor recurrence after Rx Lacks specificty, best combined with other markers/modalities

15. Prostate Specific Antigen Serine protein kinase-releasing enzyme specifically secreted by the epithelial cells of prostate Raised in benign conditions of prostate and cancer Used in screening for CaP in men over 50 Risk stratification for recurrence, surveillance following diagnosis &monitoring therapy

16. Total PSA = free PSA +bound PSA, and Higher percentage of free PSA is connected to the lower the cancer risk, >25% <10%, <10% ~50% High false positivity as raised in various types of injuries to prostatic tissue, unable to differentiate between indolent and aggressive forms of cancer

17. Lactate Dehydrogenase (LDH) Enzyme that catalyzes reversible conversion of pyruvate to lactate, isoforms LDHA, LDHB High serum LDH levels linked to poor survival (melanoma, prostate cancer, and RCC) High levels predict chemo/radiotherapy resistance Prognostic marker in metastatic cancers Can help guide therapy SCLC, testicular and GI cancer

18. CA-125 Glycosylated mucin Most important biomarker for monitoring epithelial ovarian cancer (OC), sensitivity ~70% Serum level associated with the progression and recurrence of OC <35 U/mL post surgery/chemotherapy (effective) vs ≥70 U/mL (recurrence, failure of Rx) (Gynecologic cancer group) Also in cervical, endometrial and gastric cancer Endometrosis , CAD

19. Ca-19-9 Mucin glycoprotein antigen Found in pancreatic duct, gallbladder, and gastrointestinal tract 79% sensitivity for diagnosis of pancreatic cancer Also increased in bile duct obstruction and inflammation, pancreatitis, acute diarrhea, stomach ulcer, pulmonary fibrosis Absent in individuals with Lewis allele deficiencies

20. Human Chorionic Gonadotropin Polypeptide hormone consisting of two noncovalently linked subunits (α and β). Serum levels of HCG in non-pregnant and menopausal women 5–10 U/L, and increase dramatically during pregnancy Increased serum HCG levels are observed in trophoblastic tumors for initial diagnosis and monitoring disease progression Ovarian cancer, testicular cancer, breast cancer, lung cancer, HCC, CRC, kidney cancer.

21. Tumor biomarker-based cancer therapy Targeted cancer therapy including monoclonal antibodies (mAbs) drugs specifically targeting proteins or genes in cancer cells Higher potency and lower toxicity c/w traditional chemotherapy

22. Tumor biomarker-based cancer therapy RAS inhibitors PI3K inhibitors AKT inhibitors mTor inhibitors CDK4/6 inhibitors MDM2 inhibitors Telomerase inhibitors VEGF inhibitors

23. Future directions Liquid biopsy Multi-omics integration combining genomics, proteomics and metabolomics to comprehensive biomarker discovery AI and Machine learning applications for better data analysis leading to better biomarker identification Epigenetic biomarkers: DNA methylation, histone modification and non coding RNAs Point of care testing: Portable, affordable and accessible biomarker assays