Small Molecules and Peptides Targeting Tumour Microenvironment

The tumor microenvironment (TME) is characterized by hypoxia, acidity, and a high concentration of immune and inflammatory cells. These factors taken together are critical for the genesis, progression, and resistance of tumors to therapy. The TME’s unique characteristics often hinder the efficacy of traditional cancer treatments by limiting drug access and promoting immune suppression. TME targeting has become a viable approach for effective tumor treatment. Traditional cancer therapies often struggle with penetrating and accessing cancer cells effectively. On the contrary, due to their higher accessibility and penetration, small molecule inhibitors and peptides have been thoroughly investigated and several have been effectively used in clinical settings to treat cancer. Recent efforts have focused on developing small molecule inhibitors and peptides that specifically target the TME or its components. Peptides such as RGD and NGR are specifically home to tumor vasculature, enhancing drug delivery and efficacy, while LyP-1 and LyP-2 target tumor lymphatics, demonstrating intrinsic antitumor activity. Additionally, small molecules, including hypoxia-activated prodrugs and pH-responsive drug delivery systems, exploit the TME’s abnormal conditions to selectively release cytotoxic agents. Combining these targeted strategies with existing treatments, such as immunotherapy and conventional chemotherapy. These findings highlight the potential of TME-targeting strategies to improve therapeutic outcomes and overcome limitations of conventional cancer therapies. While challenges remain in optimizing delivery and minimizing off-target effects, TME-targeting approaches hold significant potential for improving cancer treatment outcomes.