Heterotypic signaling of cancer-associated  fibroblasts in shaping the cancer cell drug resistance

Butti, Ramesh; Khaladkar, Ashwini; Bhardwaj, Priya; Prakasam, Gopinath

doi:10.20517/cdr.2022.72

Cited by 10 publications

(9 citation statements)

References 196 publications

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“…The reciprocal interaction between tumor cells and fibroblasts plays a crucial role in the progression of breast cancer [104,105]. OPN emerges as a key regulator in facilitating the crosstalk between tumor and stromal fibroblasts, contributing to breast cancer advancement [62,104,106].…”

Section: Cafmentioning

confidence: 99%

Osteopontin, a Key Multifaceted Regulator in Tumor Progression and Immunomodulation

Panda,

Mishra,

Nath

et al. 2024

Preprint

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Tumor microenvironment (TME) is composed of various cellular components such as tumor cells, stromal cells including fibroblasts, adipocytes, mast cell, lymphatic vascular cells and infiltrating immune cells, macrophages, dendritic cells and lymphocytes. The intricate interplay between these cells influences tumor growth, metastasis and therapy failure. Significant advancements in breast cancer therapy have resulted in a substantial decrease in mortality. However, existing cancer treatments frequently result in toxicity and nonspecific side effects. Therefore, improving targeted drug delivery and increasing the efficacy of drugs are crucial for enhancing the treatment outcome and reducing the burden of toxicity. In this review, we provided an overview of how tumor and stroma-derived osteopontin (OPN) plays a key role in regulating the oncogenic potential of various cancers including breast. Next, we have dissected the signalling network by which OPN regulates tumor progression through interaction with selective integrins and CD44 receptors. This review addresses the latest advancement in role of various splice variants of OPN in cancer progression and OPN-mediated tumor-stromal interaction, EMT, CSCs enhancement, immunomodulation, metastasis, chemoresistance, metabolic reprogramming and further suggest that OPN might be a potential therapeutic target and prognostic biomarker for the evolving landscape of cancer management.

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Section: Cafmentioning

confidence: 99%

Osteopontin, a Key Multifaceted Regulator in Tumor Progression and Immunomodulation

Panda,

Mishra,

Nath

et al. 2024

Preprint

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“…CAFs are represented by highly heterogeneous cell populations which account for about 50% of the total number of all TME cells ( Butti et al, 2023 ; Wieder, 2023 ). Therefore, CAFs are often defined as stromal TME cells ( De et al, 2021 ; Kochetkova and Samuel, 2021 ; Mor et al, 2022 ).…”

Section: Effects Of Radiation Therapy On Cancer-associated Fibroblast...mentioning

confidence: 99%

Dual effects of radiotherapy on tumor microenvironment and its contribution towards the development of resistance to immunotherapy in gastrointestinal and thoracic cancers

Zhao,

Mo,

Neganova

et al. 2023

Front. Cell Dev. Biol.

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Successful clinical methods for tumor elimination include a combination of surgical resection, radiotherapy, and chemotherapy. Radiotherapy is one of the crucial components of the cancer treatment regimens which allow to extend patient life expectancy. Current cutting-edge radiotherapy research is focused on the identification of methods that should increase cancer cell sensitivity to radiation and activate anti-cancer immunity mechanisms. Radiation treatment activates various cells of the tumor microenvironment (TME) and impacts tumor growth, angiogenesis, and anti-cancer immunity. Radiotherapy was shown to regulate signaling and anti-cancer functions of various TME immune and vasculature cell components, including tumor-associated macrophages, dendritic cells, endothelial cells, cancer-associated fibroblasts (CAFs), natural killers, and other T cell subsets. Dual effects of radiation, including metastasis-promoting effects and activation of oxidative stress, have been detected, suggesting that radiotherapy triggers heterogeneous targets. In this review, we critically discuss the activation of TME and angiogenesis during radiotherapy which is used to strengthen the effects of novel immunotherapy. Intracellular, genetic, and epigenetic mechanisms of signaling and clinical manipulations of immune responses and oxidative stress by radiotherapy are accented. Current findings indicate that radiotherapy should be considered as a supporting instrument for immunotherapy to limit the cancer-promoting effects of TME. To increase cancer-free survival rates, it is recommended to combine personalized radiation therapy methods with TME-targeting drugs, including immune checkpoint inhibitors.

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“…The TME components consist of an extracellular matrix (ECM) and multiple cell types including cancer‐associated fibroblasts (CAFs), tumor‐associated macrophages (TAMs), endothelial cells, and mesenchymal stem cells (MSCs) 256 . Tumor growth and progression and subsequent development of chemoresistance are mediated by the cross‐talk between tumor cells and their surrounding stromal cells via paracrine loops, chemokine networks, and cell–cell interactions 257–260 . CAFs are one of the most important nonmalignant cell populations in the TME, and they play a crucial role in cancer progression, metastasis and chemotherapy resistance 261,262 .…”

Section: Key Molecular Processes In Dtcsmentioning

confidence: 99%

Targeting drug‐tolerant cells: A promising strategy for overcoming acquired drug resistance in cancer cells

Song,

Lan,

Zheng

et al. 2023

MedComm

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Drug resistance remains the greatest challenge in improving outcomes for cancer patients who receive chemotherapy and targeted therapy. Surmounting evidence suggests that a subpopulation of cancer cells could escape intense selective drug treatment by entering a drug‐tolerant state without genetic variations. These drug‐tolerant cells (DTCs) are characterized with a slow proliferation rate and a reversible phenotype. They reside in the tumor region and may serve as a reservoir for resistant phenotypes. The survival of DTCs is regulated by epigenetic modifications, transcriptional regulation, mRNA translation remodeling, metabolic changes, antiapoptosis, interactions with the tumor microenvironment, and activation of signaling pathways. Thus, targeting the regulators of DTCs opens a new avenue for the treatment of therapy‐resistant tumors. In this review, we first provide an overview of common characteristics of DTCs and the regulating networks in DTCs development. We also discuss the potential therapeutic opportunities to target DTCs. Last, we discuss the current challenges and prospects of the DTC‐targeting approach to overcome acquired drug resistance. Reviewing the latest developments in DTC research could be essential in discovering of methods to eliminate DTCs, which may represent a novel therapeutic strategy for preventing drug resistance in the future.

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Heterotypic signaling of cancer-associated fibroblasts in shaping the cancer cell drug resistance

Cited by 10 publications

References 196 publications

Osteopontin, a Key Multifaceted Regulator in Tumor Progression and Immunomodulation

Osteopontin, a Key Multifaceted Regulator in Tumor Progression and Immunomodulation

Dual effects of radiotherapy on tumor microenvironment and its contribution towards the development of resistance to immunotherapy in gastrointestinal and thoracic cancers

Targeting drug‐tolerant cells: A promising strategy for overcoming acquired drug resistance in cancer cells

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