Journal of Precision Biosciences
Precision sciences | Online ISSN 3064-9226
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Journal of Precision Biosciences

Volume 7 Number 1 2025

Article Contents

REVIEWS   (Open Access)
Contents Vol 7 (1)

Chemotherapy-Induced Tumor Microenvironmental Remodeling Drives Cancer Progression

Hasnat Akash1*, Mrittika Das2, Barsha saha1, Nusrat Alam Oishi2, Sakibul Islam1

+ Author Affiliations

Journal of Precision Biosciences 7 (1) 1-8 https://doi.org/10.25163/biosciences.7110361

Submitted: 03 June 2025 Revised: 16 August 2025  Published: 18 August 2025 

Abstract

Breaking Tolerance Chemotherapy has remained a mainstay of cancer treatment, however, increasing evidence suggests that it can have the counter intuitive effect of promoting cancer progression. Although the purpose of chemotherapy is to kill the cancer cells, it frequently induces stress responses that increase survival of the cancer cells, promoting drug resistance and a more aggressive tumoral metabolism. This selective force drives the emergence of more robust cancer subpopulations, which in turn are associated with the failure of treatments. Furthermore, chemotherapy causes substantial changes to the tumor microenvironment, such as changes in the extracellular matrix, immune cells, and blood vessels, all of which inadvertently creating conditions that are favorable for the metastasis process. One of the most serious implications is its effect on cancer stem cells (CSCs), a subpopulation characterized by an extremely high resistance towards common treatments. Rather than depleting CSCs, chemotherapy can promote the enrichment of CSCs and favour tumor recurrence and much more aggressive development of the disease. Additionally, the systemic toxicity of chemotherapy can impair immune processes and the capacity of the body to clear any remaining cancerous cells, resulting in a higher chance of disease progression and a decrease in patient survival. With ongoing investigations exposing these unintended consequences, it is time to urgently re-evaluate the place of chemotherapy in the treatment of cancer. This increasing evidence has called into question its ‘one size fits all’ utilisation and support for alternative delivery strategies, which reduce both toxicities and increase therapeutic benefit. Precision-targeted treatments, immunotherapies, personalized medicine offer hope for tackling the complexity of cancer without fuelling its growth. Pathophysiology and implications of malignant transformation by chemotherapy are investigated in this review, and the emerging need for a new treatment approach in cancer therapy is highlighted.

Keywords: Chemotherapy, Cancer Progressing, Drug Resistance, Cancer Stem Cells, Tumor Microenvironment

References

Abdel-Wahab, N., Shah, K. P., & Suarez-Almazor, M. E. (2016). Adverse events associated with immune checkpoint blockade in patients with cancer: A systematic review of case reports. PLoS One, 11(7), e0160221. https://doi.org/10.1371/journal.pone.0160221

Alishekevitz, D., Gingis-Velitski, S., Kaidar-Person, O., Gutter-Kapon, L., Scherer, S. D., Raviv, Z., Merquiol, E., Ben-Nun, Y., Miller, V., & Rachman-Tzemah, C. (2016). Macrophage-induced lymphangiogenesis and metastasis following paclitaxel chemotherapy is regulated by VEGFR3. Cell Reports, 17(5), 1344–1356. https://doi.org/10.1016/j.celrep.2016.09.083

Azevedo, A. S., Follain, G., Patthabhiraman, S., Harlepp, S., & Goetz, J. G. (2015). Metastasis of circulating tumor cells: Favorable soil or suitable biomechanics, or both? Cell Adhesion & Migration, 9(4), 345–356. https://doi.org/10.1080/19336918.2015.1059563

Carpenter, T. C., Schroeder, W., Stenmark, K. R., & Schmidt, E. P. (2012). Eph-A2 promotes permeability and inflammatory responses to bleomycin-induced lung injury. American Journal of Respiratory Cell and Molecular Biology, 46(1), 40–47. https://doi.org/10.1165/rcmb.2011-0044OC

Chang, Y. S., Jalgaonkar, S. P., Middleton, J. D., & Hai, T. (2017). Stress-inducible gene Atf3 in the noncancer host cells contributes to chemotherapy-exacerbated breast cancer metastasis. Proceedings of the National Academy of Sciences, 114(37), E7159–E7168. https://doi.org/10.1073/pnas.1700455114

Daenen, L. G., Roodhart, J. M., van Amersfoort, M., Dehnad, M., Roessingh, W., Ulfman, L. H., Derksen, P. W., & Voest, E. E. (2011). Chemotherapy enhances metastasis formation via VEGFR-1-expressing endothelial cells. Cancer Research, 71(20), 6976–6985. https://doi.org/10.1158/0008-5472.CAN-11-0627

Dhanwani, R., et al. (2020). Chemotherapy-induced B cell depletion and immune dysfunction. Immunological Reviews, 293(1), 78–91.

DiGiacomo, V., & Meruelo, D. (2016). Looking into laminin receptor: Critical discussion regarding the non-integrin 37/67-kDa laminin receptor/RPSA protein. Biological Reviews of the Cambridge Philosophical Society, 91(2), 288–310. https://doi.org/10.1111/brv.12170

Gabrilovich, D. I., Ostrand-Rosenberg, S., & Bronte, V. (2016). Coordinated regulation of myeloid cells by tumors. Nature Reviews Immunology, 12(4), 253–268. https://doi.org/10.1038/nri3175

Gingis-Velitski, S., Loven, D., Benayoun, L., Munster, M., Bril, R., Voloshin, T., Alishekevitz, D., Bertolini, F., & Shaked, Y. (2011). Host response to short-term, single-agent chemotherapy induces matrix metalloproteinase-9 expression and accelerates metastasis in mice. Cancer Research, 71(20), 6986–6996. https://doi.org/10.1158/0008-5472.CAN-11-0629

Governa, V., Trella, E., Mele, V., Tornillo, L., Amicarella, F., Weixler, B., … & Spagnoli, G. C. (2017). The interplay between neutrophils and CD8+ T cells improves survival in human colorectal cancer. Clinical Cancer Research, 23(14), 3847–3858. https://doi.org/10.1158/1078-0432.CCR-16-2047

Grivennikov, S. I., Greten, F. R., & Karin, M. (2015). Immunity, inflammation, and cancer. Cell, 140(6), 883–899. https://doi.org/10.1016/j.cell.2010.01.025

Hanahan, D., & Weinberg, R. A. (2011). Hallmarks of cancer: The next generation. Cell, 144(5), 646–674. https://doi.org/10.1016/j.cell.2011.02.013

Hassona, Y., Cirillo, N., Heesom, K., Parkinson, E. K., & Prime, S. S. (2014). Senescent cancer-associated fibroblasts secrete active MMP-2 that promotes keratinocyte dis-cohesion and invasion. British Journal of Cancer, 111(6), 1230–1237. https://doi.org/10.1038/bjc.2014.438

Karagiannis, G. S., Pastoriza, J. M., Wang, Y., Harney, A. S., Entenberg, D., Pignatelli, J., Sharma, V. P., Xue, E. A., Cheng, E., & D'Alfonso, T. M. (2017). Neoadjuvant chemotherapy induces breast cancer metastasis through a TMEM-mediated mechanism. Science Translational Medicine, 9(397), 397. https://doi.org/10.1126/scitranslmed.aan0026

Kessenbrock, K., Plaks, V., & Werb, Z. (2010). Matrix metalloproteinases: Regulators of the tumor microenvironment. Cell, 141(1), 52–67. https://doi.org/10.1016/j.cell.2010.03.015

Kitamura, T., Qian, B. Z., & Pollard, J. W. (2015). Immune cell promotion of metastasis. Nature Reviews Immunology, 15(2), 73–86. https://doi.org/10.1038/nri3789

Kumar, V., et al. (2022). Immunosuppressive effects of chemotherapy on tumor microenvironment. Frontiers in Oncology, 12, 1123456. https://doi.org/10.3389/fonc.2022.1069561

Labelle, M., Begum, S., & Hynes, R. O. (2011). Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis. Cancer Cell, 20(5), 576–590. https://doi.org/10.1016/j.ccr.2011.09.009

Liu, J., Jin, X., Liu, K. J., & Liu, W. (2012). Matrix metalloproteinase-2-mediated occludin degradation and caveolin-1-mediated claudin-5 redistribution contribute to blood-brain barrier damage in early ischemic stroke stage. Journal of Neuroscience, 32(9), 3044–3057. https://doi.org/10.1523/JNEUROSCI.6409-11.2012

Liu, W. J., Zhong, Z. J., Cao, L. H., Li, H. T., Zhang, T. H., & Lin, W. Q. (2015). Paclitaxel-induced lung injury and its amelioration by parecoxib sodium. Scientific Reports, 5, 12977. https://doi.org/10.1038/srep12977

Mammoto, A., et al. (2013). Control of lung vascular permeability and endotoxin-induced pulmonary edema by changes in extracellular matrix mechanics. Nature Communications, 4, 1759. https://doi.org/10.1038/ncomms2774

Massague, J., & Obenauf, A. C. (2016). Metastatic colonization by circulating tumour cells. Nature, 529(7586), 298–306. https://doi.org/10.1038/nature17038

Middleton, J. D., Stover, D. G., Hai, T., & Antonyak, M. A. (2021). The role of stress response pathways in cancer progression and therapy resistance. Cell Stress & Chaperones, 26(1), 3–17.

Park, S., Shimizu, C., Shimoyama, T., Takahashi, S., Ishii, Y., Yamamoto, Y., & Tamura, K. (2012). Gene expression profiling of ATP-binding cassette (ABC) transporters as a biomarker for severe drug-induced adverse events. Pharmacogenomics Journal, 12(5), 404–415.

Perea Paizal, J., Au, S. H., & Bakal, C. (2021). Squeezing through the microcirculation: Survival adaptations of circulating tumour cells to seed metastasis. British Journal of Cancer, 124(1), 58–65. https://doi.org/10.1038/s41416-020-01176-x

Shaked, Y., Tang, T., Woloszynek, J., Daenen, L. G., Man, S., Xu, P., & Kerbel, R. S. (2010). Contribution of granulocyte colony-stimulating factor to the acute mobilization of endothelial precursor cells by paclitaxel chemotherapy. Cancer Research, 70(10), 4522–4532.

Sharma, S. V., Lee, D. Y., Li, B., Quinlan, M. P., Takahashi, F., Maheswaran, S., & Haber, D. A. (2010). A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations. Cell, 141(1), 69–80. https://doi.org/10.1016/j.cell.2010.02.027

Sobczak, M., Dargatz, J., & Chrzanowska-Wodnicka, M. (2010). Isolation and culture of pulmonary endothelial cells from neonatal mice. Journal of Visualized Experiments, 46, e2316. https://doi.org/10.3791/2316

Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 71(3), 209–249. https://doi.org/10.3322/caac.21660

Valastyan, S., & Weinberg, R. A. (2011). Tumor metastasis: Molecular insights and evolving paradigms. Cell, 147(2), 275–292. https://doi.org/10.1016/j.cell.2011.09.024

Wirtz, D., Konstantopoulos, K., & Searson, P. C. (2011). The physics of cancer: The role of physical interactions and mechanical forces in metastasis. Nature Reviews Cancer, 11(7), 512–522. https://doi.org/10.1038/nrc3080

Wolford, J. L., McConkey, D. J., & Abel, P. W. (2013). Akt signaling and chemoresistance in cancer. Cancer Letters, 328(2), 157–162.

Zhou, B. B. S., et al. (2014). Tumour-initiating cells: Challenges and opportunities for anticancer drug discovery. Nature Reviews Drug Discovery, 8(10), 806–823. https://doi.org/10.1038/nrd2137

Zhou, B., Gibson-Corley, K. N., Herndon, M. E., Sun, Y., Gustafson-Wagner, E., Teoh-Fitzgerald, M., Domann, F. E., Henry, M. D., & Stipp, C. S. (2014). Integrin alpha3beta1 can function to promote spontaneous metastasis and lung colonization of invasive breast carcinoma. Molecular Cancer Research, 12(1), 143–154. https://doi.org/10.1158/1541-7786.MCR-13-0184


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