Role of the tumor microenvironment in regulating apoptosis and cancer progression

Cancer Lett. 2016 Aug 10;378(2):150-9. doi: 10.1016/j.canlet.2016.05.012. Epub 2016 May 17.


Apoptosis is a gene-directed program that is engaged to efficiently eliminate dysfunctional cells. Evasion of apoptosis may be an important gate to tumor initiation and therapy resistance. Like any other developmental program, apoptosis can be disrupted by several genetic aberrations driving malignant cells into an uncontrolled progression and survival. For its sustained growth, cancer develops in a complex environment, which provides survival signals and rescues malignant cells from apoptosis. Recent studies have clearly shown a wide interaction between tumor cells and their microenvironment, confirming the influence of the surrounding cells on tumor expansion and invasion. These non-malignant cells not only intensify tumor cells growth but also upgrade the process of metastasis. The strong crosstalk between malignant cells and a reactive microenvironment is mediated by soluble chemokines and cytokines, which act on tumor cells through surface receptors. Disturbing the microenvironment signaling might be an encouraging approach for patient's treatment. Therefore, the ultimate knowledge of "tumor-microenvironment" interactions facilitates the identification of novel therapeutic procedures that mobilize cancer cells from their supportive cells. This review focuses on cancer progression mediated by the dysfunction of apoptosis and by the fundamental relationship between tumor and reactive cells. New insights and valuable targets for cancer prevention and therapy are also presented.

Keywords: Apoptosis; Immune escape; Inflammation; Microenvironment; Resistance.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Apoptosis Regulatory Proteins / metabolism
  • Apoptosis* / drug effects
  • Cell Proliferation
  • Disease Progression
  • Humans
  • Inflammation Mediators / metabolism
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Receptors, Immunologic / metabolism
  • Signal Transduction
  • Tumor Escape
  • Tumor Microenvironment*


  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • Inflammation Mediators
  • Receptors, Immunologic