Novel targeting approaches and signaling pathways of colorectal cancer: An insight

Abstract

Colorectal cancer (CRC) is the third most common cancer of mortality in the world. Chemotherapy based treatment leads to innumerable side effects as it delivers the anticancer drug to both normal cells besides cancer cells. Sonic Hedgehog (SHH), Wnt wingless-type mouse mammary tumor virus/β-catenin, transforming growth factor-β/SMAD, epidermal growth factor receptor and Notch are the main signaling pathways involved in the progression of CRC. Targeted therapies necessitate information regarding the particular aberrant pathways. Advancements in gene therapies have resulted in the recognition of novel therapeutic targets related with these signal-transduction cascades. CRC is a step-wise process where mutations occur over the time and activation of oncogenes and deactivation of tissue suppressor genes takes place. Genetic changes which are responsible for the induction of carcinogenesis include loss of heterozygosity in tumor suppressor genes such as adenomatous polyposis coli, mutation or deletion of genes like p53 and K-ras. Therefore, many gene-therapy approaches like gene correction, virus-directed enzyme-prodrug therapy, immunogenetic manipulation and virotherapy are currently being explored. Development of novel strategies for the safe and effective delivery of drugs to the cancerous site is the need of the hour. This editorial accentuates different novel strategies with emphasis on gene therapy and immunotherapy for the management of CRC.

Comprehensive review of targeted therapy for colorectal cancer

“…2). 27,28 Given the complex downstream signaling and difficulties in completely inhibiting specific biological interactions, not all existing CRC-related pathways can be successfully interfered with, and current data cover only a few pathways in which experimentally identified targeted agents can be proved to be efficient in clinical studies, and a large group of targeted drugs remain in preclinical status or in phase I trials.…”

TERT-mediated induction of MIR500A contributes to tumor invasiveness by targeting Hedgehog pathway

“…A high-stage of gastric cancer and negative PTCH1 staining have been identified as unfavorable risk factor for overall survival (438) and it has been described an important role of Hh signaling in bladder cancer growth and tumorigenicity (39). In addition, Shh signaling crosstalks with other signaling pathways during development and cancer progression, such as Notch, Wnt, and TGF-β signaling pathways (40), which are also regulated by MIR500A (26) and TERT (6). Therefore, our results support that the MIR500A is also a good therapeutic target to fight cancer.…”

Multifaceted Roles of TRIM Proteins in Colorectal Carcinoma

“…PI3K phosphorylates phosphatidylinositol 4,5-bisphosphate (PIP2) to yield phosphatidylinositol 3,4,5-triphosphate (PIP3) and synthesis of this lipids leads to the recruitment of the serine/threonine kinase Akt, synonymously called protein kinase B (PKB), the downstream target of PI3K ( Figure 3 B). Phosphorylation of Akt by the phosphoinositide dependent protein kinase 1 (PDK1) functionally associated with tumor growth and inhibition of apoptosis is also relevant for EMT ( Figure 3 B) [ 13 , 122 ]. The PI3K pathway is antagonized by intrinsic inhibitors including the lipid phosphatase and tensin homologue protein (PTEN) which dephosphorylates PIP3 to PIP2 ( Figure 3 B).…”