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Malachite Green Assay for the Discovery of Heat-Shock Protein 90 Inhibitors

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Published on: January 20, 2023

Crossroad between the Heat Shock Protein and Inflammation Pathway in Acquiring Drug Resistance: A Possible Target for

Prathap Somu¹, Nagaraj Basavegowda², Levin Anbu Gomez³

¹Department of Biotechnology and Chemical Engineering, School of Civil & Chemical Engineering, Manipal University Jaipur, Dehmi Kalan, Jaipur 303007, India.

|October 28, 2023

Abstract:

The development of multidrug resistance (MDR) against chemotherapeutic agents has become a major impediment in cancer therapy. Understanding the underlying mechanism behind MDR can guide future treatment for cancer with better therapeutic outcomes. Recent studies evidenced that crossroads interaction between the heat shock proteins (HSP) and inflammatory responses under the tumor microenvironment plays a pivotal role in modulating drug responsiveness and drug resistance through a complex cytological process. This review aims to investigate the interrelationship between inflammation and HSP in acquiring multiple drug resistance and investigate strategies to overcome the drug resistance to improve the efficacy of cancer treatment. HSP plays a dual regulatory effect as an immunosuppressive and immunostimulatory agent, involving the simultaneous blockade of multiple signaling pathways in acquiring MDR. For example, HSP27 shows biological effects on monocytes by causing IL10 and TNFα secretion and blocking monocyte differentiation to normal dendritic cells and tumor-associated macrophages to promote cancer progression and chemoresistance. Thus, the HSP function and immune-checkpoint release modalities provide a therapeutic target for a therapeutically beneficial approach for enhancing anti-tumor immune responses. The interconnection between inflammation and HSP, along with the tumor microenvironment in acquiring drug resistance, has become crucial for rationalizing the effect of HSP immunomodulatory activity with immune checkpoint blockade. This relationship can overcome drug resistance and assist in the development of novel combinatorial cancer immunotherapy in fighting cancer with decreasing mortality rates.

Insights

Heat shock proteins (HSP) and inflammation interact within the tumor microenvironment, driving multidrug resistance (MDR) in cancer. Targeting this interplay offers new strategies to overcome chemoresistance and enhance immunotherapy for better cancer treatment outcomes.

Area of Science:

Oncology
Immunology
Molecular Biology

Background:

Multidrug resistance (MDR) significantly hinders effective cancer chemotherapy.
The tumor microenvironment, involving heat shock proteins (HSP) and inflammation, critically influences drug response.
Understanding the interplay between HSP and inflammatory pathways is key to overcoming treatment resistance.

Purpose of the Study:

To review the intricate relationship between inflammation and HSP in the development of MDR.
To explore therapeutic strategies targeting the HSP-inflammation axis to enhance cancer treatment efficacy.
To investigate how HSP's immunomodulatory functions can be leveraged with immune checkpoint blockade.

Main Methods:

Literature review focusing on studies investigating HSP, inflammation, and drug resistance in cancer.
Analysis of the dual role of HSP as both immunosuppressive and immunostimulatory agents.
Examination of specific HSPs, like HSP27, and their effects on immune cells and cancer progression.

Main Results:

HSP and inflammation collaboratively promote MDR through complex cellular mechanisms.
HSP27 influences monocyte differentiation and cytokine secretion (IL10, TNFα), fostering chemoresistance.
HSP's immunomodulatory activities present viable therapeutic targets, especially when combined with immune checkpoint inhibitors.

Conclusions:

The crosstalk between inflammation and HSP in the tumor microenvironment is central to acquiring drug resistance.
Targeting HSP functions and immune checkpoints offers a promising approach to enhance anti-tumor immunity.
Combinatorial therapies involving HSP modulation and immune checkpoint blockade hold potential for improving cancer treatment and reducing mortality.

Read full analysis

Keywords:

cancer heat shock proteins immunomodulatory effect interleukin multidrug resistance tumor microenvironment

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