Small molecule inhibitors targeting the cancers

Abstract

Compared with traditional therapies, targeted therapy has merits in selectivity, efficacy, and tolerability. Small molecule inhibitors are one of the primary targeted therapies for cancer. Due to their advantages in a wide range of targets, convenient medication, and the ability to penetrate into the central nervous system, many efforts have been devoted to developing more small molecule inhibitors. To date, 88 small molecule inhibitors have been approved by the United States Food and Drug Administration to treat cancers. Despite remarkable progress, small molecule inhibitors in cancer treatment still face many obstacles, such as low response rate, short duration of response, toxicity, biomarkers, and resistance. To better promote the development of small molecule inhibitors targeting cancers, we comprehensively reviewed small molecule inhibitors involved in all the approved agents and pivotal drug candidates in clinical trials arranged by the signaling pathways and the classification of small molecule inhibitors. We discussed lessons learned from the development of these agents, the proper strategies to overcome resistance arising from different mechanisms, and combination therapies concerned with small molecule inhibitors. Through our review, we hoped to provide insights and perspectives for the research and development of small molecule inhibitors in cancer treatment.

BDH1‐mediated LRRC31 regulation dependent on histone lysine β‐hydroxybutyrylation to promote lung adenocarcinoma progression

“…Small‐molecule inhibitors play a crucial role in combining protein targets to control the proliferation, survival, apoptosis, and differentiation of malignant tumors, offering convenience and effectiveness, particularly for patients with specific genetic alterations or distinct characteristics. Notably, mutations in EGFR tyrosine kinases are pivotal in NSCLC progression, 45 establishing inhibitors targeting EGFR tyrosine kinase as the primary treatment for NSCLC carrying EGFR exon 19 deletion or exon 21 mutation 25 . Nevertheless, the emergence of acquired drug resistance has diminished the efficacy of numerous drugs, 46 underscoring the pressing need for alternative dosing regimens in these cases.…”

“…Hence, it is imperative to identify new indicators and strategies to combat LUAD. Small‐molecule inhibitors, which function by binding to the target protein's surface “pocket” to inhibit its function, are the primary agents used in targeted LUAD therapy 25 . STAT3 plays a pivotal role as an oncogene in the progression of non‐small cell lung cancer (NSCLC) 26 .…”

“…Small-molecule inhibitors, which function by binding to the target protein's surface "pocket" to inhibit its function, are the primary agents used in targeted LUAD therapy. 25 STAT3 plays a pivotal role as an oncogene in the progression of non-small cell lung cancer (NSCLC). 26 Zheng et al 27 discovered that the combination of the STAT3 inhibitor W2014-S with gefitinib exhibited promising efficacy in NSCLC xenografts resistant to EGFR tyrosine kinase inhibitors.…”

Therapeutic strategies for EGFR-mutated non-small cell lung cancer patients with osimertinib resistance

“…Generally, surgical resection is considered the standard procedure for earlystage NSCLC, while chemotherapy is widely applied in advanced NSCLC patients. In particular, molecular targeted therapy regimens are routinely recommended to treat NSCLC patients harboring corresponding genetic mutations [3,4]. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are given priority for those with EGFR-sensitizing mutations, including EGFR exon 19 deletion (Ex19del) and L858R mutations [5,6].…”

An MMAE-loaded PDL1 active targeting nanomedicine for the precision treatment of colon cancer

“…7,8 Tumoractive-targeting drugs through ligands that are responsive to the tumor microenvironment (TME), [9][10][11][12][13][14] on the other hand, have significantly improved the tumor delivery efficiency of drugs by actively recognizing tumors. These include small molecule targeted agents, 15,16 monoclonal antibodies, 17,18 antibody-drug conjugates, 19,20 and targeted nano-delivery systems. 21,22 Among them, antibody-drug conjugates (ADCs), known as "magic bullets", have been extensively studied and have shown remarkable efficacy.…”