Combinatorial therapy in tumor microenvironment: Where do we stand?

Kumari, Smita; Advani, Dia; Sharma, Sudhanshu; Ambasta, Rashmi K.; Kumar, Pravir

doi:10.1016/j.bbcan.2021.188585

Cited by 69 publications

(47 citation statements)

References 390 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been well proved that TME not only plays an important role in the occurrence, development and metastasis of tumors [ 4 , 5 ], but also induces resistance to conventional anticancer treatments such as radiotherapy and chemotherapy, resulting in poor prognosis [ 5 , 6 ]. Nevertheless, TME could also be exploited to realize certain specific cancer treatments owing to its notable difference to normal tissues [ 7 ]. In addition, normalization of TME may in turn improve tumor therapy outcome [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

A tumor microenvironment-responsive poly(amidoamine) dendrimer nanoplatform for hypoxia-responsive chemo/chemodynamic therapy

et al. 2022

View full text Add to dashboard Cite

Background Chemodynamic therapy is a promising cancer treatment with specific therapeutic effect at tumor sites, as toxic hydroxyl radical (·OH) could only be generated by Fenton or Fenton-like reaction in the tumor microenvironment (TME) with low pH and high level of endogenous hydrogen peroxide. However, the low concentration of catalytic metal ions, excessive glutathione (GSH) and aggressive hypoxia at tumor site seriously restrict the curative outcomes of conventional chemodynamic therapy. Results In this study, polyethylene glycol-phenylboronic acid (PEG-PBA)-modified generation 5 (G5) poly(amidoamine) (PAMAM) dendrimers were synthesized as a targeted nanocarrier to chelate Cu(II) and then encapsulate hypoxia-sensitive drug tirapazamine (TPZ) by the formation of hydrophobic Cu(II)/TPZ complex for hypoxia-enhanced chemo/chemodynamic therapy. The formed G5.NHAc-PEG-PBA@Cu(II)/TPZ (GPPCT) nanoplatform has good stability and hemocompatibility, and could release Cu(II) ions and TPZ quickly in weakly acidic tumor sites via pH-sensitive dissociation of Cu(II)/TPZ. In vitro experiments showed that the GPPCT nanoplatforms can efficiently target murine breast cancer cells (4T1) cells overexpressing sialic acid residues, and show a significantly enhanced inhibitory effect on hypoxic cells by the activation of TPZ. The excessive GSH in tumors could be depleted by the reduction of Cu(II) to Cu(I), and abundant of toxic ·OH would be generated in tumor cells by Fenton reaction for chemodynamic therapy. In vivo experiments demonstrated that the GPPCT nanoplatform could specifically accumulate at tumors, effectively inhibit the growth and metastasis of tumors by the combination of CDT and chemotherapy, and be metabolized with no systemic toxicity. Conclusions The targeted GPPCT nanoplatform may represent an effective model for the synergistic inhibition of different tumor types by hypoxia-enhanced chemo/chemodynamic therapy. Graphical Abstract

show abstract

Section: Introductionmentioning

confidence: 99%

A tumor microenvironment-responsive poly(amidoamine) dendrimer nanoplatform for hypoxia-responsive chemo/chemodynamic therapy

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Tumor cells and microenvironment cooperate to create an immunosuppressive milieu that promotes tumor development and metastasis and generates a systemic immunosuppressive status, detrimental for the patient. The understanding of these biological-immune mechanisms is crucial to maximize the efficacy of combination therapies for designing patient-tailored approaches ( 1 , 2 ).…”

Section: Introductionmentioning

confidence: 99%

Immunogenic Cell Death and Immunomodulatory Effects of Cabozantinib

et al. 2021

View full text Add to dashboard Cite

Cabozantinib (XL-184) is a multitarget tyrosine kinase inhibitor (TKI) targeting receptor tyrosine kinases (RTKs) involved in oncogenesis and angiogenesis. It is currently the standard therapy for medullary thyroid cancer (MTC), metastatic renal cell carcinoma (mRCC), and hepatocellular carcinoma (HCC). Combination of Cabozantinib with immunotherapy is now a standard treatment in metastatic renal cancer, and its efficacy is being tested in ongoing clinical trial in prostate cancer patients. Here, we report that Cabozantinib may exert an immunostimulatory role by inducing immunogenic stress of prostate cancer cells and directly modulating dendritic cells (DCs). Cabozantinib treatment arrested the cell cycle and triggered immunogenic cell death (ICD) in prostate cancer cells in vitro. Cabozantinib had a direct effect on DCs by the down-modulation of β-catenin and change in migratory and costimulatory phenotype of the DCs. These results may suggest possible immunomodulatory effects induced by Cabozantinib that could be exploited to optimize patient-tailored immunotherapeutic treatments.

show abstract

“…TME is the microenvironment on which tumor cells grow and immune cells exert their anti-tumor effects [ 46 ]. Immune cells in TME play a very important role in the occurrence and development of tumors.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of PD-L1 expression, tumor-infiltrating lymphocytes, and tumor microenvironment in LUAD: differences between Asians and Caucasians

et al. 2021

View full text Add to dashboard Cite

Backgrounds The characteristics of programmed cell death protein-1 (PD-L1) expression, tumor-infiltrating lymphocytes (TILs), and tumor microenvironment (TME) in lung adenocarcinoma (LUAD) patients are closely related to immunotherapy, and there are differences between Asians and Caucasians. Methods Acquire the transcriptome data of the Cancer Genome Atlas and Chinese LUAD patients. R software was used to analyze the differential expression of genes, prognosis, and gene function. Use CIBERSORT for TIL-related analysis and ESTIMATE for TME-related analysis. Results The expression of PD-L1 in tumor tissues of Caucasian LUAD patients was lower than that in normal tissues, while there was no significant difference in Asians. There was no statistical difference between PD-L1 expression and prognosis. The composition of TILs between Caucasian and Asian LUAD patients was quite different. There was no correlation between TILs and prognosis in Caucasians. However, the higher content of resting mast cells indicated a better prognosis in Asians. The Caucasian patients with higher immune and estimate scores had a better prognosis (p = 0.021, p = 0.025). However, the Asian patients with a higher estimate score had a worse prognosis (p = 0.024). The high expression of COL5A2 (p = 0.046, p = 0.027) and NOX4 (p = 0.020, p = 0.019) were both associated with the poor prognosis in Caucasians and Asians. Conclusion There are many differences in the characteristics of PD-L1 expression, TILs, and TME between Caucasian and Asian LUAD patients. This provides a certain hint for the selection of specific immunotherapy strategies separately for Caucasian and Asian LUAD patients.

show abstract

Combinatorial therapy in tumor microenvironment: Where do we stand?

Cited by 69 publications

References 390 publications

A tumor microenvironment-responsive poly(amidoamine) dendrimer nanoplatform for hypoxia-responsive chemo/chemodynamic therapy

A tumor microenvironment-responsive poly(amidoamine) dendrimer nanoplatform for hypoxia-responsive chemo/chemodynamic therapy

Immunogenic Cell Death and Immunomodulatory Effects of Cabozantinib

Comprehensive analysis of PD-L1 expression, tumor-infiltrating lymphocytes, and tumor microenvironment in LUAD: differences between Asians and Caucasians

Contact Info

Product

Resources

About