Adebayo Amusa S, Agbaje Kafilat, Adesina Simeon K, Olajubutu Oluwabukunmi
College of Pharmacy, Howard University, 2400 6th St NW, Washington, DC 20059, USA.
Pharmaceutics. 2023 Nov 12;15(11):2620. doi: 10.3390/pharmaceutics15112620.
Colorectal cancer (CRC) is one of the deadliest malignancies in the US, ranking fourth after lung, prostate, and breast cancers, respectively, in general populations. It continues to be a menace, and the incidence has been projected to more than double by 2035, especially in underdeveloped countries. This review seeks to provide some insights into the disease progression, currently available treatment options and their challenges, and future perspectives. Searches were conducted in the PubMed search engine in the university's online library. The keywords were "Colorectal Cancer" AND "disease process" OR "disease mechanisms" OR "Current Treatment" OR "Prospects". Selection criteria were original articles published primarily during the period of 2013 through 2023. Abstracts, books and documents, and reviews/systematic reviews were filtered out. Of over 490 thousand articles returned, only about 800 met preliminary selection criteria, 200 were reviewed in detail, but 191 met final selection criteria. Fifty-one other articles were used due to cross-referencing. Although recently considered a disease of lifestyle, CRC incidence appears to be rising in countries with low, low-medium, and medium social demographic indices. CRC can affect all parts of the colon and rectum but is more fatal with poor disease outcomes when it is right-sided. The disease progression usually takes between 7-10 years and can be asymptomatic, making early detection and diagnosis difficult. The CRC tumor microenvironment is made up of different types of cells interacting with each other to promote the growth and proliferation of the tumor cells. Significant advancement has been made in the treatment of colorectal cancer. Notable approaches include surgery, chemotherapy, radiation therapy, and cryotherapy. Chemotherapy, including 5-fluorouracil, irinotecan, oxaliplatin, and leucovorin, plays a significant role in the management of CRC that has been diagnosed at advanced stages. Two classes of monoclonal antibody therapies have been approved by the FDA for the treatment of colorectal cancer: the vascular endothelial growth factor (VEGF) inhibitor, e.g., bevacizumab (Avastin), and the epidermal growth factor receptor (EGFR) inhibitor, e.g., cetuximab (Erbitux) and panitumumab (Verbitix). However, many significant problems are still being experienced with these treatments, mainly off-target effects, toxic side effects, and the associated therapeutic failures of small molecular drugs and the rapid loss of efficacy of mAb therapies. Other novel delivery strategies continue to be investigated, including ligand-based targeting of CRC cells.
结直肠癌(CRC)是美国最致命的恶性肿瘤之一,在普通人群中分别仅次于肺癌、前列腺癌和乳腺癌,位列第四。它仍然是一个威胁,预计到2035年发病率将增加一倍以上,尤其是在欠发达国家。本综述旨在对该疾病的进展、目前可用的治疗方案及其挑战以及未来前景提供一些见解。在大学在线图书馆的PubMed搜索引擎中进行了检索。关键词为“结直肠癌”以及“疾病过程”或“疾病机制”或“当前治疗”或“前景”。选择标准为主要在2013年至2023年期间发表的原创文章。摘要、书籍和文献以及综述/系统评价被筛选掉。在返回的超过49万篇文章中,只有约800篇符合初步选择标准,对200篇进行了详细审查,但191篇符合最终选择标准。由于交叉引用,还使用了另外51篇文章。尽管结直肠癌最近被认为是一种生活方式疾病,但在社会人口统计学指数低、中低和中等的国家,其发病率似乎正在上升。结直肠癌可影响结肠和直肠的所有部位,但右侧发病时疾病结局更致命。疾病进展通常需要7至10年,且可能无症状,这使得早期检测和诊断变得困难。结直肠癌肿瘤微环境由相互作用以促进肿瘤细胞生长和增殖的不同类型细胞组成。结直肠癌的治疗取得了重大进展。显著的方法包括手术、化疗、放疗和冷冻疗法。化疗,包括5-氟尿嘧啶、伊立替康、奥沙利铂和亚叶酸钙,在晚期诊断的结直肠癌管理中发挥着重要作用。两类单克隆抗体疗法已被美国食品药品监督管理局(FDA)批准用于治疗结直肠癌:血管内皮生长因子(VEGF)抑制剂,如贝伐单抗(阿瓦斯汀),以及表皮生长因子受体(EGFR)抑制剂,如西妥昔单抗(爱必妥)和帕尼单抗(维必施)。然而,这些治疗仍然存在许多重大问题,主要是脱靶效应、毒副作用以及小分子药物相关的治疗失败和单克隆抗体疗法疗效的迅速丧失。其他新型递送策略仍在研究中,包括基于配体的结直肠癌细胞靶向。