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Advances in Chemotherapy: Mechanisms, Efficacy, and Side Effects

Chemotherapy and Immunogenic Cell Death (ICD)

Chemotherapy has long been a cornerstone in cancer treatment, effectively suppressing tumor growth through various mechanisms. Notably, certain chemotherapeutic agents such as doxorubicin (DOX), oxaliplatin (OXA), cyclophosphamide (CPA), and paclitaxel (PTX) not only kill cancer cells but also induce immunogenic cell death (ICD). This process triggers the release of danger signals and tumor-associated antigens (TAAs), which stimulate antigen-presenting cells (APCs) and initiate robust antitumor immune responses. This dual action enhances the overall efficacy of chemotherapy and has paved the way for chemo-immunotherapy, a promising combination therapy that leverages both chemotherapy and immunotherapy to combat malignant tumors .

Chemo-Immunotherapy: A Synergistic Approach

Chemo-immunotherapy combines traditional chemotherapy with immunotherapy to enhance cancer treatment efficacy. This approach benefits from the immune-modulatory properties of certain chemotherapeutic drugs, which can potentiate immune checkpoint inhibitor (ICI)-based therapies. Recent studies have shown that combining chemotherapy with ICIs can significantly improve treatment outcomes in various cancers, including melanoma and lung cancer. The use of nano-based drug delivery systems (NDDS) further enhances this approach by providing targeted delivery, tumor microenvironment response, and site-specific release, thereby reducing side effects and optimizing clinical outcomes.

Chemotherapy-Induced Side Effects

Despite its effectiveness, chemotherapy is notorious for its severe side effects, which can significantly impact patients' quality of life. Common side effects include neurotoxicity, which affects both the peripheral and central nervous systems, leading to conditions such as neuropathic pain, chemobrain, and enteric neuropathy. Doxorubicin, a widely used chemotherapeutic agent, has been linked to cognitive impairments, commonly referred to as "chemo-brain." A meta-analysis revealed significant impairments in global cognition, executive function, language, memory, and processing speed in doxorubicin-treated patients.

Chemoprevention and Precision Medicine

Chemoprevention involves using pharmacologic or natural agents to prevent cancer development. Recent advances have led to the synthesis of new drugs targeting specific molecular pathways involved in carcinogenesis. For instance, agents like tamoxifen and 13-cis-retinoic acid have shown clinical efficacy in preventing cancer, particularly in high-risk patients. Aspirin has also emerged as a potential chemopreventive agent for colorectal cancer, although its long-term use requires careful consideration due to associated risks.

Optimizing Chemotherapy Regimens

The efficacy of chemotherapy can be influenced by the choice of drug, dosage, and treatment schedule. A proposed strategy, termed medium-dose intermittent chemotherapy (MEDIC), involves administering chemotherapeutic agents intermittently at intermediate doses. This approach aims to maximize cytotoxic damage to tumors while sustaining anti-tumor immune responses, thereby enhancing overall treatment efficacy. Additionally, studies comparing perioperative chemotherapy with preoperative chemotherapy and postoperative chemoradiotherapy in gastric cancer patients have highlighted the need for optimizing preoperative treatment strategies to improve survival outcomes.

Conclusion

Chemotherapy remains a vital component of cancer treatment, with ongoing research focused on enhancing its efficacy and reducing its side effects. The integration of immunotherapy, the development of precision chemoprevention strategies, and the optimization of chemotherapy regimens are promising avenues for improving patient outcomes. As our understanding of the mechanisms underlying chemotherapy-induced side effects deepens, new interventions can be developed to mitigate these adverse effects and improve the quality of life for cancer patients.