Qayum Arem, Shah Syed Mohmad, Singh Shashank K
Cancer Pharmacology Division, Indian Institute of Integrative Medicine, CSIR, Jammu, India,
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India.
Cell Physiol Biochem. 2022 Apr 25;56(2):180-208. doi: 10.33594/000000512.
Cancer is a chaos of uncontrolled cell proliferation that has consistently invented new circuitry programs to operate inside the cell machinery. Globally, cancer statistics account for 65% of mortality worldwide, mainly due to the adoption of lifestyle behaviours. In 2020, FDA approved 40 new drugs, out of which 16 (40%) were approved as cancer drugs. Overall, the risk of dying from cancer decreased, but further reductions in cancer death rates can be accelerated by applying existing cancer control knowledge across all the population segments, emphasising those in the lowest socio-economic and other disadvantaged population. Various therapeutic regimes, including low-molecular-weight inhibitors, targeting oncogenic signaling pathways are under development. However, the pitfall of targeted therapies is the quick emergence of acquired drug resistance encumbered with toxic side effects. Several FDA acclaimed therapeutic legacies or biosimilars earmarked signaling pathways of rare diseases (cystic fibrosis, erythropoietic protoporphyria, neuromyelitis optica spectrum disorder, tenosynovial giant cell tumor, sickle cell disease, systemic sclerosis-associated interstitial lung disease, muscular dystrophy), neurological and psychiatric disorders, infectious diseases, heart, lung, circulatory, endocrine diseases, autoimmune conditions, cancers and blood disorders. When cancer progresses, these signals develop specific characteristics that can be targeted for anti-cancer therapy. The designer inhibitors have emerged as novel pharmaceutical interventions that aim to block the pathways in an effort to reverse the abnormal phenotype of the cancer cells. Numerous cell-signaling channels have evolved and invigorated to make off three-dimensional feedback networks. The magnitude of accessible information by pathways occupies curated information as a consortium. To fully appreciate the pivotal roles that signaling cascades play in tumor development, it is necessary to understand the involved signaling cascades in the interaction between cancer cells. The prime endeavour is to canonically curate all signaling pathways involving cell cycle, EGFR, MAPK, GPCR, PI3K/ AKT/mTOR, immune checkpoints, nuclear receptors, janus kinase, transcription activators etc., involving the manipulation of genetic and nuclear receptors. Here, we will summarize the vast amount of information describing the signals that mediate crosstalk between cancer cells and the targets related to this crosstalk.
癌症是细胞不受控制地增殖的一种紊乱状态，它不断创造出新的信号通路程序在细胞机制内运行。在全球范围内，癌症统计数据占全球死亡率的65%，主要归因于生活方式行为。2020年，美国食品药品监督管理局（FDA）批准了40种新药，其中16种（40%）被批准为抗癌药物。总体而言，死于癌症的风险有所降低，但通过在所有人群中应用现有的癌症控制知识，尤其是那些社会经济地位最低和其他弱势群体，可以加速癌症死亡率的进一步降低。包括低分子量抑制剂在内的各种针对致癌信号通路的治疗方案正在研发中。然而，靶向治疗的缺陷是会迅速出现获得性耐药，并伴有毒副作用。几种FDA认可的治疗药物或生物类似物针对罕见疾病（囊性纤维化、红细胞生成性原卟啉症、视神经脊髓炎谱系障碍、腱鞘巨细胞瘤、镰状细胞病、系统性硬化症相关间质性肺病、肌肉萎缩症）、神经和精神疾病、传染病、心脏、肺、循环、内分泌疾病、自身免疫性疾病、癌症和血液疾病的信号通路。当癌症进展时，这些信号会产生可用于抗癌治疗的特定特征。设计抑制剂已成为新型药物干预手段，旨在阻断这些通路，以逆转癌细胞的异常表型。众多细胞信号通道不断演变并活跃起来，形成三维反馈网络。各通路可获取的信息量作为一个整体占据了经过整理的信息。为了充分理解信号级联在肿瘤发展中所起的关键作用，有必要了解癌细胞间相互作用中涉及的信号级联。首要任务是规范整理所有涉及细胞周期、表皮生长因子受体（EGFR）、丝裂原活化蛋白激酶（MAPK）、G蛋白偶联受体（GPCR）、磷脂酰肌醇-3激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白（PI3K/AKT/mTOR）、免疫检查点、核受体、janus激酶、转录激活因子等的信号通路，包括对基因和核受体的调控。在此，我们将总结大量描述介导癌细胞间串扰的信号以及与此串扰相关靶点的信息。
