Table 1.

The role of HSP and inflammatory tumor microenvironment supporting tumor progression and acquiring drug resistance.

Inflammatory Tumor Microenvironment and HSP Supporting Tumor Formation and Progression	The Role of HSP and Inflammatory Tumor Microenvironment Supporting the Acquiring Drug Resistance
Tumor microenvironment remodeling by recruitment of leukocytes, lymphocytes, expression of tumor-promoting chemokines, cytokines, and induction of an angiogenic switch.	Overexpressed pro-inflammatory cytokine-like IL-8 helps in the acquisition of the chemoresistance reported against cisplatin and paclitaxel by increasing expression of both MDR1 and apoptosis inhibitory proteins (Bcl-2, Bcl-xL, and XIAP), and the activation of PI3 K/Akt and Ras/MEK/ERK signaling.
Activated inflammatory cells serve as sources of reactive nitrogen intermediates (RNI) and reactive oxygen species (ROS) for inducing DNA damage and genomic instability essential for cancer progression.	Difference in pharmacokinetics and pharmacodynamics of drugs in vitro and in vivo.
Tumor-promoting cytokines production like TNF-α activates the transcription factors, in pre-malignant cells such as NF-κB, STAT3, and AP-1, and induces genes to stimulate cell proliferation and survival.	The expression of stress-inducible HSP inhibition of apoptosis in both the intrinsic and extrinsic pathways at multiple points like HSP70 inhibits Bax activation and blocks the permeabilization mitochondrial membrane in the intrinsic pathway, thereby proapoptotic factors release. Whereas HSP70 stops the death-inducing signaling complex assembly (DISC) in the extrinsic pathway
Extensive stress-inducible HSP production in cancer for regulating highly rewired metabolic stress