Medicine:Recurrent cancer

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Short description: Reoccurrence of cancer


Recurrent cancer is a form of cancer that has returned or recurred when a fraction of primary tumor cells evade the effects of treatment and survive in small spaces that are undetectable by diagnostic tests. The initial tumor may become the site of cancer’s return or it may spread to another part of the body.[1] These surviving cells accumulate various genetic changes over time, eventually producing a new tumor cell. It can take up to weeks, months, or even years for cancer to return. Following surgery and/or chemotherapy or radiotherapy, certain tumor cells may persist and develop resistance to treatment and eventually develop into new tumors. Age, sex, cancer type, treatment duration, stage of advancement, and grade of original tumor are some of the factors that determine the rate of cancer recurrence.[2][3] If recurrent cancer has already moved to other body parts or has developed chemo-resistance then it may be more aggressive than original cancer. In general, the severity of cancer increases with a shorter duration of time between initial treatment and its return.[3]

Cancers with the highest recurrence rates include Glioblastoma with a recurrence rate of almost 100%[4],  Epithelial ovarian cancer with a recurrence rate of 85%,[5] and Bladder cancer with a recurrence rate of 30-54%[6]

Types

There are three types of recurrent cancers:

  • Local Recurrence - Cancer returns to the same original site.[7][8]
  • Regional Recurrence - Cancer is detected in tissue or lymph nodes near the original site.[9]
  • Distant Recurrence - Cancer has been detected in tissue far from the original site. Also known as metastatic recurrence.[10][11]

Causes

Cancer Stem Cells

Cancer stem cells (CSC) are a small population of the entire tumor cell mass, that are responsible for early formation, progression, and recurrence of cancer. It also contributes to drug resistance.[12][13] CSCs are thought to originate from normal stem cells, progenitor cells or differentiated cells as a result of cumulative genetic mutation and subsequent genomic instability.[14] They are found in the tumor microenvironment's specialized niches. CSCs have so far been found in a variety of tumors, including those of the brain, breast, ovary, head and neck, etc..[15][16][17][18][19]

CSCs have the ability of self-proliferation just like regular stem cells. A single CSC can divide asymmetrically into one CSC and one differentiated tumor cell. The tumor is majority made up of the latter cells.[20]

In some cancers CSCs are quiescent for long period of time, making them ineffective to the treatment. Therefore, even decades after the primary cancer has been fully treated, the reactivation of the inactive CSCs may lead to tumor recurrence.[21][22]

Neosis

Hypoxia, chemotherapeutic agents, and radiation can generate Polyploid Giant Cancer Cells (PGCC). Some PGCCs have the ability to undergo neosis, which is characterized by nuclear budding karyokinesis, asymmetric intracellular cytokinesis and the generation of Raju cells, which are tiny mononuclear cells having stem cell like characteristics. These cells play a role in cancer recurrence and therapy resistance.[23]

Phoenix Rising

Phoenix rising is a process by which dead cells send signals that promote growth and division, generating new cells.[24] After a tissue injury, stem cells present in and around the injured tissue play a crucial role in replenishing the damaged ones. It is theorized that molecules released from wounded cells trigger stem cells' migration to that site, followed by differentiation and proliferation.[25] Through the process of apoptosis, the dying tumor cells provide growth signals and repair radiation-damaged tumors. PGE2 is released by apoptotic cells in a caspase-dependent manner, which aids cancer stem cells and cancer progenitor cells in expanding and multiplying.[26]

Diagnosis

Early diagnosis of recurrence is important and can improve the prognosis and survival of patients with cancer.[27] Depending on the primary cancer type, several laboratory and imaging tests, as well as numerous invasive procedures, are used for the diagnosis of recurring cancers.[28][29] Malignant tumors develop and secrete biologic chemicals known as tumor markers that are detectable in the bloodstream. These markers might ideally be used to screen for cancer, diagnose it, and track how effectively it responds to treatment.[30]

Treatment

The inherent limits of current cancer therapy approaches usually result in treatment failure. Chemotherapy and radiation therapy resistance is a common factor in the failure of treatment for many cancers.[31] Additionally, because most treatments cannot completely eradicate CSCs, many methods that are not adequately selective against CSCs might be harmful to healthy tissues, and patients frequently run the risk of recurrence and metastasis.[32]

Recent years have seen the development of numerous treatments with the goal of eliminating CSC. Targeting CSC surface markers, the ABC cascade, the microenvironment, or signal cascades could all help kill CSCs. There are numerous drugs targeting these markers or pathways, which are being tested in clinical trials. The treatment varies from cancer to cancer and patient to patient.[33][34][35][36]

References

  1. ↑ "https://www.cancer.gov/publications/dictionaries/cancer-terms/def/recurrent-cancer" (in en). 2011-02-02. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/recurrent-cancer. 
  2. ↑ Baker, Frank; Denniston, Maxine; Smith, Tenbroeck; West, Michele M. (2005). "Adult cancer survivors: How are they faring?". Cancer 104 (S11): 2565–2576. doi:10.1002/cncr.21488. ISSN 0008-543X. PMID 16258929. http://dx.doi.org/10.1002/cncr.21488. 
  3. ↑ 3.0 3.1 "Cancer Recurrence - Why Does Cancer Come Back" (in en). 2021-07-15. https://www.cancercenter.com/cancer-recurrence. 
  4. ↑ van Linde, Myra E.; Brahm, Cyrillo G.; de Witt Hamer, Philip C.; Reijneveld, Jaap C.; Bruynzeel, Anna M. E.; Vandertop, W. Peter; van de Ven, Peter M.; Wagemakers, Michiel et al. (2017-10-01). "Treatment outcome of patients with recurrent glioblastoma multiforme: a retrospective multicenter analysis" (in en). Journal of Neuro-Oncology 135 (1): 183–192. doi:10.1007/s11060-017-2564-z. ISSN 1573-7373. PMID 28730289. PMC 5658463. https://doi.org/10.1007/s11060-017-2564-z. 
  5. ↑ Corrado, Giacomo; Salutari, Vanda; Palluzzi, Eleonora; Distefano, Maria Grazia; Scambia, Giovanni; Ferrandina, Gabriella (2017-12-02). "Optimizing treatment in recurrent epithelial ovarian cancer". Expert Review of Anticancer Therapy 17 (12): 1147–1158. doi:10.1080/14737140.2017.1398088. ISSN 1473-7140. PMID 29086618. https://doi.org/10.1080/14737140.2017.1398088. 
  6. ↑ Mari, Andrea; Campi, Riccardo; Tellini, Riccardo; Gandaglia, Giorgio; Albisinni, Simone; Abufaraj, Mohammad; Hatzichristodoulou, Georgios; Montorsi, Francesco et al. (2018-02-01). "Patterns and predictors of recurrence after open radical cystectomy for bladder cancer: a comprehensive review of the literature" (in en). World Journal of Urology 36 (2): 157–170. doi:10.1007/s00345-017-2115-4. ISSN 1433-8726. PMID 29147759. PMC 5799348. https://doi.org/10.1007/s00345-017-2115-4. 
  7. ↑ Mahvi, David A.; Liu, Rong; Grinstaff, Mark W.; Colson, Yolonda L.; Raut, Chandrajit P. (November 2018). "Local Cancer Recurrence: The Realities, Challenges, and Opportunities for New Therapies: XXXX" (in en). CA: A Cancer Journal for Clinicians 68 (6): 488–505. doi:10.3322/caac.21498. PMID 30328620. 
  8. ↑ Abulafi, A M; Williams, N S (January 1994). "Local recurrence of colorectal cancer: The problem, mechanisms, management and adjuvant therapy". British Journal of Surgery 81 (1): 7–19. doi:10.1002/bjs.1800810106. ISSN 0007-1323. PMID 8313126. http://dx.doi.org/10.1002/bjs.1800810106. 
  9. ↑ Ritoe, Savitri C.; Verbeek, André L. M.; Krabbe, Paul F. M.; Kaanders, Johannes H. A. M.; van den Hoogen, Frank J. A.; Marres, Henri A. M. (2007). "Screening for local and regional cancer recurrence in patients curatively treated for laryngeal cancer: Definition of a high-risk group and estimation of the lead time". Head & Neck 29 (5): 431–438. doi:10.1002/hed.20534. ISSN 1043-3074. PMID 17120311. http://dx.doi.org/10.1002/hed.20534. 
  10. ↑ Lehnert, T.; Rudek, B.; Buhl, K.; Golling, M. (2002-06-01). "Surgical therapy for loco-regional recurrence and distant metastasis of gastric cancer" (in en). European Journal of Surgical Oncology 28 (4): 455–461. doi:10.1053/ejso.2002.1260. ISSN 0748-7983. PMID 12099659. https://www.sciencedirect.com/science/article/pii/S0748798302912606. 
  11. ↑ Varlotto, John M.; Recht, Abram; Flickinger, John C.; Medford-Davis, Laura N.; Dyer, Ann M.; DeCamp, Malcolm M. (2009-03-01). "Factors associated with local and distant recurrence and survival in patients with resected nonsmall cell lung cancer". Cancer 115 (5): 1059–1069. doi:10.1002/cncr.24133. ISSN 0008-543X. PMID 19152440. 
  12. ↑ Pang, Lisa Y.; Argyle, David (July 2010). "Cancer stem cells and telomerase as potential biomarkers in veterinary oncology". The Veterinary Journal 185 (1): 15–22. doi:10.1016/j.tvjl.2010.04.008. ISSN 1090-0233. PMID 20580998. http://dx.doi.org/10.1016/j.tvjl.2010.04.008. 
  13. ↑ Visvader, Jane E.; Lindeman, Geoffrey J. (June 2012). "Cancer Stem Cells: Current Status and Evolving Complexities". Cell Stem Cell 10 (6): 717–728. doi:10.1016/j.stem.2012.05.007. ISSN 1934-5909. PMID 22704512. 
  14. ↑ Peitzsch, Claudia; Tyutyunnykova, Anna; Pantel, Klaus; Dubrovska, Anna (June 2017). "Cancer stem cells: The root of tumor recurrence and metastases". Seminars in Cancer Biology 44: 10–24. doi:10.1016/j.semcancer.2017.02.011. ISSN 1044-579X. PMID 28257956. http://dx.doi.org/10.1016/j.semcancer.2017.02.011. 
  15. ↑ Al-Hajj, Muhammad; Wicha, Max S.; Benito-Hernandez, Adalberto; Morrison, Sean J.; Clarke, Michael F. (April 2003). "Prospective identification of tumorigenic breast cancer cells" (in en). Proceedings of the National Academy of Sciences 100 (7): 3983–3988. doi:10.1073/pnas.0530291100. ISSN 0027-8424. PMID 12629218. Bibcode: 2003PNAS..100.3983A. 
  16. ↑ Pang, Lisa Y.; Cervantes-Arias, Alejandro; Else, Rod W.; Argyle, David J. (2011-03-30). "Canine Mammary Cancer Stem Cells are Radio- and Chemo- Resistant and Exhibit an Epithelial-Mesenchymal Transition Phenotype". Cancers 3 (2): 1744–1762. doi:10.3390/cancers3021744. ISSN 2072-6694. PMID 24212780. 
  17. ↑ Wang, Xin; Venugopal, Chitra; Singh, Sheila K. (2011), "Cancer Stem Cells in Brain Cancer", Cancer Stem Cells in Solid Tumors (Totowa, NJ: Humana Press): pp. 37–56, doi:10.1007/978-1-61779-246-5_3, ISBN 978-1-61779-245-8, http://dx.doi.org/10.1007/978-1-61779-246-5_3, retrieved 2022-10-07 
  18. ↑ Major, Aidan G.; Pitty, Luke P.; Farah, Camile S. (2013-03-03). "Cancer Stem Cell Markers in Head and Neck Squamous Cell Carcinoma" (in en). Stem Cells International 2013: e319489. doi:10.1155/2013/319489. ISSN 1687-966X. PMID 23533441. 
  19. ↑ Rizzo, S.; Attard, G.; Hudson, D. L. (December 2005). "Prostate epithelial stem cells". Cell Proliferation 38 (6): 363–374. doi:10.1111/j.1365-2184.2005.00356.x. ISSN 0960-7722. PMID 16300650. PMC 6496238. http://dx.doi.org/10.1111/j.1365-2184.2005.00356.x. 
  20. ↑ Jordan, Craig T.; Guzman, Monica L.; Noble, Mark (2006-09-21). "Cancer Stem Cells". New England Journal of Medicine 355 (12): 1253–1261. doi:10.1056/nejmra061808. ISSN 0028-4793. PMID 16990388. http://dx.doi.org/10.1056/nejmra061808. 
  21. ↑ Allan, Alison L.; Vantyghem, Sharon A.; Tuck, Alan B.; Chambers, Ann F. (2007-04-12). "Tumor Dormancy and Cancer Stem Cells: Implications for the Biology and Treatment of Breast Cancer Metastasis". Breast Disease 26 (1): 87–98. doi:10.3233/bd-2007-26108. ISSN 1558-1551. PMID 17473368. http://dx.doi.org/10.3233/bd-2007-26108. 
  22. ↑ Ojha, Rani; Bhattacharyya, Shalmoli; Singh, Shrawan K. (December 2015). "Autophagy in Cancer Stem Cells: A Potential Link Between Chemoresistance, Recurrence, and Metastasis". BioResearch Open Access 4 (1): 97–108. doi:10.1089/biores.2014.0035. ISSN 2164-7860. PMID 26309786. PMC 4497670. http://dx.doi.org/10.1089/biores.2014.0035. 
  23. ↑ Zhang, Zhengxiang; Feng, Xiao; Deng, Zheng; Cheng, Jin; Wang, Yiwei; Zhao, Minghui; Zhao, Yucui; He, Sijia et al. (August 2021). "Irradiation‐induced polyploid giant cancer cells are involved in tumor cell repopulation via neosis" (in en). Molecular Oncology 15 (8): 2219–2234. doi:10.1002/1878-0261.12913. ISSN 1574-7891. PMID 33523579. 
  24. ↑ Pang, Lisa Y.; Hurst, Emma A.; Argyle, David J. (2016). "Cyclooxygenase-2: A Role in Cancer Stem Cell Survival and Repopulation of Cancer Cells during Therapy". Stem Cells International 2016: 1–11. doi:10.1155/2016/2048731. ISSN 1687-966X. PMID 27882058. 
  25. ↑ Boland, K; Flanagan, L; Prehn, J HM (July 2013). "Paracrine control of tissue regeneration and cell proliferation by Caspase-3". Cell Death & Disease 4 (7): e725. doi:10.1038/cddis.2013.250. ISSN 2041-4889. PMID 23846227. PMC 3730423. http://dx.doi.org/10.1038/cddis.2013.250. 
  26. ↑ Zimmerman, Mary A.; Huang, Qian; Li, Fang; Liu, Xinjiang; Li, Chuan-Yuan (October 2013). "Cell Death–Stimulated Cell Proliferation: A Tissue Regeneration Mechanism Usurped by Tumors During Radiotherapy". Seminars in Radiation Oncology 23 (4): 288–295. doi:10.1016/j.semradonc.2013.05.003. ISSN 1053-4296. PMID 24012343. PMC 3891050. http://dx.doi.org/10.1016/j.semradonc.2013.05.003. 
  27. ↑ Schneble, Erika J.; Graham, Lindsey J.; Shupe, Matthew P.; Flynt, Frederick L.; Banks, Kevin P.; Kirkpatrick, Aaron D.; Nissan, Aviram; Henry, Leonard et al. (2014). "Current Approaches and Challenges in Early Detection of Breast Cancer Recurrence". Journal of Cancer 5 (4): 281–290. doi:10.7150/jca.8016. ISSN 1837-9664. PMID 24790656. PMC 3982041. http://dx.doi.org/10.7150/jca.8016. 
  28. ↑ Israel, Ora; Kuten, Abraham (2007-01-01). "Early Detection of Cancer Recurrence: 18F-FDG PET/CT Can Make a Difference in Diagnosis and Patient Care" (in en). Journal of Nuclear Medicine 48 (1 suppl): 28S–35S. ISSN 0161-5505. PMID 17204718. https://jnm.snmjournals.org/content/48/1_suppl/28S. 
  29. ↑ Panebianco, Valeria; Barchetti, Flavio; Musio, Daniela; De Felice, Francesca; Proietti, Camilla; Indino, Elena Lucia; Megna, Valentina; Schillaci, Orazio et al. (2014-03-13). "Advanced Imaging for the Early Diagnosis of Local Recurrence Prostate Cancer after Radical Prostatectomy" (in en). BioMed Research International 2014: e827265. doi:10.1155/2014/827265. ISSN 2314-6133. PMID 24757679. 
  30. ↑ Sauter, Edward R. (2017-10-01). "Reliable Biomarkers to Identify New and Recurrent Cancer". European Journal of Breast Health 13 (4): 162–167. doi:10.5152/ejbh.2017.3635. ISSN 2587-0831. PMID 29082372. 
  31. ↑ Zhao, Jihe (April 2016). "Cancer stem cells and chemoresistance: The smartest survives the raid". Pharmacology & Therapeutics 160: 145–158. doi:10.1016/j.pharmthera.2016.02.008. ISSN 0163-7258. PMID 26899500. PMC 4808328. http://dx.doi.org/10.1016/j.pharmthera.2016.02.008. 
  32. ↑ Abdullah, Lissa Nurrul; Chow, Edward Kai‐Hua (2013-01-17). "Mechanisms of chemoresistance in cancer stem cells". Clinical and Translational Medicine 2 (1): 3. doi:10.1186/2001-1326-2-3. ISSN 2001-1326. PMID 23369605. 
  33. ↑ Chen, Ke; Huang, Ying-hui; Chen, Ji-long (2013-05-20). "Understanding and targeting cancer stem cells: therapeutic implications and challenges". Acta Pharmacologica Sinica 34 (6): 732–740. doi:10.1038/aps.2013.27. ISSN 1671-4083. PMID 23685952. PMC 3674516. http://dx.doi.org/10.1038/aps.2013.27. 
  34. ↑ Yang, Liqun; Shi, Pengfei; Zhao, Gaichao; Xu, Jie; Peng, Wen; Zhang, Jiayi; Zhang, Guanghui; Wang, Xiaowen et al. (2020-02-07). "Targeting cancer stem cell pathways for cancer therapy". Signal Transduction and Targeted Therapy 5 (1): 8. doi:10.1038/s41392-020-0110-5. ISSN 2059-3635. PMID 32296030. PMC 7005297. http://dx.doi.org/10.1038/s41392-020-0110-5. 
  35. ↑ Yoshida, Go J.; Saya, Hideyuki (2015-10-21). "Therapeutic strategies targeting cancer stem cells". Cancer Science 107 (1): 5–11. doi:10.1111/cas.12817. ISSN 1347-9032. PMID 26362755. PMC 4724810. http://dx.doi.org/10.1111/cas.12817. 
  36. ↑ Mambet, Cristina; Chivu-Economescu, Mihaela; Matei, Lilia; Necula, Laura Georgiana; Dragu, Denisa Laura; Bleotu, Coralia; Diaconu, Carmen Cristina (2018-06-26). "Murine models based on acute myeloid leukemia-initiating stem cells xenografting". World Journal of Stem Cells 10 (6): 57–65. doi:10.4252/wjsc.v10.i6.57. ISSN 1948-0210. PMID 29988882. 



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