Tumor Microenvironment – Selective Pressures Boosting Cancer Progression
- 220 Downloads
In 2018, 9.6 million deaths from cancer were estimated, being this disease the second leading cause of death worldwide. Notwithstanding all the efforts developed in prevention, diagnosis and new treatment approaches, chemoresistance seems to be inevitable, leading to cancer progression, recurrence and affecting the outcome of the disease. As more and more evidence support that cancer is an evolutionary and ecological process, this concept is rarely applied in the clinical context. In fact, cancer cells emerge and progress within an ecological niche – the tumor microenvironment – that is shared with several other cell types and that is continuously changing. Therefore, the tumor microenvironment imposes several selective pressures on cancer cells such as acidosis, hypoxia, competition for space and resources, immune predation and anti-cancer therapies, that cancer cells must be able to adapt to or will face extinction.
In here, the role of the tumor microenvironment selective pressures on cancer progression will be discussed, as well as the targeting of its features/components as strategies to fight cancer.
KeywordsCancer Evolution Microenvironment Metabolic selection
The authors acknowledge iNOVA4Health – UID/Multi/04462/2013, a program financially supported by Fundação para a Ciência e Tecnologia/Ministério da Educação e Ciência, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement.
- Albano G, Giorno V, Saturnino C (2007) A prey-predator model for immune response and drug resistance in tumor growth. In: Moreno Díaz R, Pichler FQAA (eds) Computer aided systems theory – EUROCAST 2007. Lecture notes in computer science, vol 4739. Springer, Berlin/Heidelberg, pp 171–178Google Scholar
- Darwin C (1859) The origin of species (text). Pennsylvania State University 448 p. https://doi.org/10.5117/9781904633785
- De Kruijf EM, Van Nes JGH, Van De Velde CJH et al (2011) Tumor-stroma ratio in the primary tumor is a prognostic factor in early breast cancer patients, especially in triple-negative carcinoma patients. Breast Cancer Res Treat 125:687–696. https://doi.org/10.1007/s10549-010-0855-6CrossRefPubMedGoogle Scholar
- Fitzgerald DM, Hastings PJ, Rosenberg SM (2017) Stress-induced mutagenesis: implications in cancer and drug resistance. Ann Rev Cancer Biol 1:119–140. https://doi.org/10.1146/annurev-cancerbio-050216-121919CrossRefGoogle Scholar
- Gallaher JA, Enriquez-Navas PM, Luddy KA et al (2017) Spatial heterogeneity and evolutionary dynamics modulate time to recurrence in continuous and adaptive cancer therapies. bioRxiv:1–21. https://doi.org/10.1101/128959
- Hicks KC, Knudson KM, Jones FR, et al (2018, April 14–18) Abstract 1740: epigenetic reprogramming of the tumor microenvironment by entinostat increases tumor sensitivity to multivalent immunotherapy combinations with an IL-15 superagonist plus vaccine or immune checkpoint blockade. In: AACR annual meeting 2018. Chicago, p 1740Google Scholar
- Ibrahim-Hashim A, Gillies RJ, Brown JS, Gatenby RA (2017) Coevolution of tumor cells and their microenvironment: “niche construction in Cancer” In: Ujvari B, Roche B, Thomas F (eds) Ecology and evolution of cancer. Elsevier Inc., pp 111–117Google Scholar
- Levayer R (2019) Solid stress, competition for space and cancer: the opposing roles of mechanical cell competition in tumour initiation and growth. Semin Cancer Biol:1–12. https://doi.org/10.1016/j.semcancer.2019.05.004
- Martín-Pardillos A, Valls-Chiva A, Serrano EB, et al (2018, April 14–18) Abstract 2183: clonal cooperation in cancer progression: a new paradigm in cancer. In: AACR annual meeting 2018. Chicago. p 2183Google Scholar
- Nagraj J, Mukherjee S, Chowdhury R (2015) Cancer: an evolutionary perspective. J Cancer Biol Res 3:1064–1068Google Scholar
- Niehr F, Eder T, Pilz T et al (2018) Multilayered omics-based analysis of a head and neck Cancer model of cisplatin resistance reveals intratumoral heterogeneity and treatment-induced clonal selection. Clin Cancer Res 24:158–168. https://doi.org/10.1158/1078-0432.CCR-17-2410CrossRefPubMedGoogle Scholar
- Odunsi K (2018) Abstract IA22: reprogramming the tumor microenvironment and T cells for ovarian cancer immunotherapy. In: AACR special conference: addressing critical questions in ovarian Cancer research and treatment; October 1-4, 2017; Pittsburgh, PA. p IA22Google Scholar