Targeting tumor microenvironment to curb chemoresistance via novel drug delivery strategies

INTRODUCTION: Tumor is a heterogeneous mass of malignant cells co-existing with non-malignant cells. This co-existence evolves from the initial developmental stages of the tumor and is one of the hallmarks of cancer providing a protumorigenic niche known as tumor microenvironment (TME). Proliferation, invasiveness, metastatic potential and maintenance of stemness through cross-talk between tumors and its stroma forms the basis of TME. AREAS COVERED: The article highlights the developmental phases of a tumor from dysplasia to the formation of clinically detectable tumors. The authors discuss the mechanistic stages involved in the formation of TME and its contribution in tumor outgrowth and chemoresistance. The authors have reviewed various approaches for targeting TME and its hallmarks along with their advantages and pitfalls. The authors also highlight cancer stem cells (CSCs) that are resistant to chemotherapeutics and thus a primary reason for tumor recurrence thereby, posing a challenge for the oncologists. EXPERT OPINION: Recent understanding of the cellular and molecular mechanisms involved in acquired chemoresistance has enabled scientists to target the tumor niche and TME and modulate and/or disrupt this communication leading to the transformation from a tumor-supportive niche environment to a tumor-non-supporting environment and give synergistic results towards an effective management of cancer.