Design Strategies and Mechanisms of Action of Small Molecule Drugs for Cancer Treatment

Abstract

Global cancer incidence continues to rise. According to the World Health Organization in 2022, there will be over 20 million new cancer cases and over 10 million deaths worldwide. Cancer has become a major public health threat to human health. Although surgery, chemotherapy, radiotherapy, and immunotherapy are currently mainstream treatments, they have significant limitations: surgery struggles to eliminate micrometastases and is only suitable for early-stage, localized tumors; chemotherapy drugs such as cisplatin are prone to severe side effects such as bone marrow suppression and nausea and vomiting, and cannot accurately distinguish between tumors and normal cells; radiotherapy relies on radiation to kill tumors, but it can easily damage the skin, mucous membranes, and internal organs in the irradiated area; and immunotherapies such as PD-1 inhibitors, while able to activate the body's immune response, only produce sustained efficacy in 20%-30% of patients and carry the risk of immune-related adverse reactions. Small molecule drugs (molecular weight <1000 Daltons) have become a core force in cancer treatment due to their unique advantages: they are easily absorbed by the intestine after oral administration and have strong tissue penetration, allowing them to directly reach tumor tissue and penetrate cell membranes to act on intracellular targets. Their relatively simple chemical structure allows for mass production through chemical synthesis, resulting in significantly lower production costs than large molecule drugs. Currently, over 150 small molecule anticancer drugs have been approved for marketing worldwide, covering a variety of cancer types, including lung cancer, leukemia, and breast cancer. Imatinib, among others, has increased the five-year survival rate of patients with chronic myeloid leukemia from 30% to over 90%, marking a milestone in targeted cancer therapy. This article systematically reviews the definition and characteristics of small molecule drugs, deeply analyzes design strategies based on target structure, biological activity, and innovative directions, and explains their mechanisms of action in inhibiting tumor cell proliferation, inducing tumor cell apoptosis, blocking tumor angiogenesis, and modulating the tumor immune microenvironment. It also summarizes the current challenges in R&D, drawing on the technical support system. This paper provides theoretical references for the R&D optimization and clinical application of small molecule drugs, and contributes to the advancement of precision cancer treatment.