title: From molecular insight to therapeutic strategy: The holistic approach for treating triple negative breast cancer.
abstract: Aim of the present study was to analyze the molecular pathogenesis of TNBC, therapeutic practice, challenges, and future goals in treatment strategies. Based on the alterations of distinct pathways, Lehmann's subgroups of TNBCs were further categorized. Those with defective DNA damage repair and replication pathways, viz. Basal Like 1 & 2 (BL1, BL2) were found susceptible to DNA intercalating drugs while those with upregulated cell signalling & motility (mesenchymal (M), mesemchymal stem like (MSL)), cell survival (BL2, M, MSL), angiogenesis (BL2, MSL), T cell signalling (Immunomodulatory/IM) pathways required targeted therapies. Our Meta-analysis categorized 12 randomized previous trial cases, solely under the following drug regimens: [1] DNA destabilizers, [2] PARP inhibitors, [3] Microtubule stabilizers, [4] Angiogenesis inhibitors, [5] Antimetabolite, [6] T cell targeted therapy; as single or combinational therapy. Best therapeutic efficacies of DNA destabilizers with angiogenesis inhibitors in combination than monotherapy with either (OR: 5.011-7.286; p value<0.001) indicated a significant prevalence of BL1 type TNBCs in populations. Statistical significance with antimetabolites as combination therapy (OR: 2.343; p value: 0.018) and not with microtubule stabilizer (OR: 0.377) were observed. Thus, for best ORR in TNBC, personalized medicine should be the therapeutic choice for the clinicians.
authors.affiliation: Dept. of Molecular Biology, Netaji Subhash Chandra Bose Cancer Research Institute, 16A Park Lane, Kolkata 700016, India.
authors.forename: Rittwika
authors.initials: R
authors.lastname: Bhattacharya
authors.affiliation: Dept. of Molecular Biology, Netaji Subhash Chandra Bose Cancer Research Institute, 16A Park Lane, Kolkata 700016, India.
authors.forename: Koyel
authors.initials: K
authors.lastname: Banerjee
authors.affiliation: National Institute for Cellular Biotechnology, Dublin, Ireland.
authors.forename: Nupur
authors.initials: N
authors.lastname: Mukherjee
authors.affiliation: Dept. of Molecular Biology, Netaji Subhash Chandra Bose Cancer Research Institute, 16A Park Lane, Kolkata 700016, India.
authors.forename: Minakshi
authors.initials: M
authors.lastname: Sen
authors.affiliation: Department of Hemato-Oncology, Netaji Subhas Chandra Bose Cancer Research Institute, 16 A Park Lane, Kolkata, 700016, India. Electronic address: hmcwt@dataone.in.
authors.forename: Ashis
authors.initials: A
authors.lastname: Mukhopadhyay
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D057285:Precision Medicine; D015398:Signal Transduction; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
keywords: BC; BL1; BL2; HR; IM; LAR; M; MSL; ORR; UNS; pCR