Editing Chemotherapy (section)

== Limitations ==
Chemotherapy does not always work, and even when it is useful, it may not completely destroy the cancer. People frequently fail to understand its limitations. In one study of people who had been newly diagnosed with incurable, [[Stage-4 cancer|stage 4 cancer]], more than two-thirds of people with lung cancer and more than four-fifths of people with colorectal cancer still believed that chemotherapy was likely to cure their cancer.<ref name=Weeks>{{cite journal | vauthors = Weeks JC, Catalano PJ, Cronin A, Finkelman MD, Mack JW, Keating NL, Schrag D | title = Patients' expectations about effects of chemotherapy for advanced cancer | journal = The New England Journal of Medicine | volume = 367 | issue = 17 | pages = 1616–25 | date = October 2012 | pmid = 23094723 | pmc = 3613151 | doi = 10.1056/NEJMoa1204410 }}</ref>

The [[blood–brain barrier]] poses an obstacle to delivery of chemotherapy to the [[brain]]. This is because the brain has an extensive system in place to protect it from harmful chemicals. Drug transporters can pump out drugs from the brain and brain's blood vessel cells into the [[cerebrospinal fluid]] and blood circulation. These transporters pump out most chemotherapy drugs, which reduces their efficacy for treatment of brain tumors. Only small [[lipophilic]] [[alkylating agents]] such as [[lomustine]] or [[temozolomide]] are able to cross this blood–brain barrier.<ref name="pmid17363519">{{cite journal | vauthors = Deeken JF, Löscher W | title = The blood-brain barrier and cancer: transporters, treatment, and Trojan horses | journal = Clinical Cancer Research | volume = 13 | issue = 6 | pages = 1663–74 | date = March 2007 | pmid = 17363519 | doi = 10.1158/1078-0432.CCR-06-2854 | doi-access = free }}</ref><ref name="pmid10794805">{{cite journal | vauthors = Agarwala SS, Kirkwood JM | title = Temozolomide, a novel alkylating agent with activity in the central nervous system, may improve the treatment of advanced metastatic melanoma | journal = The Oncologist | volume = 5 | issue = 2 | pages = 144–51 | year = 2000 | pmid = 10794805 | doi = 10.1634/theoncologist.5-2-144 | s2cid = 25331035 | doi-access = free }}</ref><ref name="pmid17538177">{{cite journal | vauthors = Gerstner ER, Fine RL | title = Increased permeability of the blood-brain barrier to chemotherapy in metastatic brain tumors: establishing a treatment paradigm | journal = Journal of Clinical Oncology | volume = 25 | issue = 16 | pages = 2306–12 | date = June 2007 | pmid = 17538177 | doi = 10.1200/JCO.2006.10.0677 }}</ref>

[[Blood vessel]]s in tumors are very different from those seen in normal tissues. As a tumor grows, tumor cells furthest away from the blood vessels become low in oxygen ([[Tumor hypoxia|hypoxic]]). To counteract this they then signal for new blood vessels to grow. The newly formed tumor vasculature is poorly formed and does not deliver an adequate blood supply to all areas of the tumor. This leads to issues with drug delivery because many drugs will be delivered to the tumor by the [[circulatory system]].<ref name="pmid16862189">{{cite journal | vauthors = Minchinton AI, Tannock IF | title = Drug penetration in solid tumours | journal = Nature Reviews. Cancer | volume = 6 | issue = 8 | pages = 583–92 | date = August 2006 | pmid = 16862189 | doi = 10.1038/nrc1893 | s2cid = 42818461 }}</ref>