Transcription Factor Networks as Targets for Therapeutic Intervention of Cancer: The Breast Cancer Paradigm

Identifying Druggable Targets by Protein Microenvironments Matching: Application to Transcription Factors

“…Transcription factors have structurally and functionally distinct domains, including nuclear‐hormone receptor, dimerization, DNA binding, nuclear localization, and regulatory domains. The plethora of genomic alterations in cancer that directly involve transcription factors highlights the potential of transcription factors as anticancer drug targets 23 , 24 . However, with the exception of drugs targeting transcription factors of the nuclear‐hormone‐receptor receptor family (tamoxifen targeting to estrogen receptor, alitretinoin to retinoic acid receptor α (RAR‐α), and thiazolidinedione to peroxisome proliferator–activated receptor γ (PPAR‐γ)), most transcription factors are considered undruggable by conventional drug discovery methods.…”

Focus on the glycerophosphocholine pathway in choline phospholipid metabolism of cancer

“…Carcinogenesis is characterized by a gradual accumulation of critical genetic and epigenetic changes, leading to initially precancerous lesions that gradually evolve into aggressive cancers . There are several oncogenic transcription factors, signal transducers and transcription activators that are hyperactivated in cancer, including activator protein (AP)‐1, nuclear factor (NF)‐κB, and signal transducer and activator of transcription (STAT)‐3 and STAT‐5, respectively . Oncogenic transcription factors participate in the initiation and progression of cancer, as well as in the development of therapy resistance .…”

“…There are several oncogenic transcription factors, signal transducers and transcription activators that are hyperactivated in cancer, including activator protein (AP)‐1, nuclear factor (NF)‐κB, and signal transducer and activator of transcription (STAT)‐3 and STAT‐5, respectively . Oncogenic transcription factors participate in the initiation and progression of cancer, as well as in the development of therapy resistance . There are also tumor‐suppressing transcription factors that are underactivated in cancer, including p53 and retinoblastoma protein (pRb), however, not much information is available as to how to stimulate or stabilize them for the purpose of therapy .…”

“…An important oncogenic transcription factor is AP‐1, which is a dimeric protein with basic leucine zipper (bZIP), dimerization and DNA‐binding domains . AP‐1 is involved in various aspects of tumorigenesis, including enhanced proliferation, suppression of apoptosis, neoangiogenesis and modulation of extracellular matrix (ECM) components .…”

Tackling the cancer signal transduction “Labyrinth”: A combinatorial use of biochemical tools with mathematical models will enhance the identification of optimal targets for each molecular defect

“…Signaling molecules and network perturbations are the mediators of these events leading to carcinogenic features, such as uncontrolled proliferation, apoptosis escape, neoangiogenesis, migration, and metastasis. In the last decade, it has been shown that a wide gamut of signal transduction molecules and oncogenic transcription factors are implicated in human tumorigenesis . Most of these proteins contribute both to initiation and progression of carcinogenesis and to the development of resistance to currently used therapeutic strategies (eg, chemotherapy, hormonal therapy, molecularly‐targeted agents, and radiotherapy).…”