22IN - Targeting the host in TNBC

Date 30 September 2012
Event ESMO Congress 2012
Session How to integrate new drugs in the current therapeutic landscape of metastatic triple negative breast cancer
Topics Breast Cancer, Metastatic
Pathology/Molecular Biology
Presenter Giuseppe Curigliano
Authors G. Curigliano
  • Medicine, Istituto Europeo di Oncologia, 20141 - Milano/IT

Abstract

Cancer medicine is increasingly moving toward a new era of personalized therapeutics that embraces integrative approaches. Combinatorial strategies will target not only cancer cell-intrinsic pathways, but also cancer cell-extrinsic cells, pathways, and mediators of the tumor microenvironment. As the strategic goal of defining the roles of the tumor microenvironment in primary and metastatic tumor progression, new discoveries can be envisioned to produce innovative multitargeting strategies that will be able to more thoroughly extinguish primary and metastatic disease, overcoming adaptive resistance mechanisms to such therapies. The cancer microenvironment is constituted of non-transformed host stromal cells such as endothelial cells,fibroblasts, various immune cells, and a complex extracellular matrix secreted by both the normal and neoplastic cells embedded in it. The importance of the microenvironment and its potential in cancer therapy is just being established. Among modalities that target the microenvironment, harnessing immune responses has long been pursued. Efforts to turn on the immune system against cancers with inactivated tumor vaccines or intratumor injections of bacterial products to induce local inflammation and recruit an antitumor immune response have led to anecdotal successes. A major limitation of the various approaches to turning on an immune response to cancer is that the immune system exerts a major effort to avoid immune over-activation, which could harm healthy tissues. Cancer takes advantage of this ability to hide from the immune system by exploiting a series of immune escape mechanisms that were developed to avoid autoimmunity (mechanisms of tolerance). Among these mechanisms are the hijacking of immune-cell–intrinsic checkpoints that are induced on T-cell activation. Blockade of one of these checkpoints, cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) or the programmed death 1 (PD-1) receptor, provided the first evidence of activity of an immune-modulation approach in the treatment of a solid tumor. The future frontier in the treatment of cancer requires identification of potential targets in order to personalize therapies. The immune system remembers what it targets, so once the system is correctly activated, it may mediate a durable tumor response.

Disclosure

The author has declared no conflicts of interest.