How does chemotherapy work to treat cancer?
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How Chemotherapy Works to Treat Cancer
Introduction to Chemotherapy in Cancer Treatment
Chemotherapy is a cornerstone in the treatment of cancer, providing curative and palliative benefits across various cancer types. It involves the use of chemical substances to kill or inhibit the growth of cancer cells. The effectiveness of chemotherapy varies depending on the type and stage of cancer, as well as the patient's overall health1 2.
Mechanisms of Action: Targeting Cancer Cells
Cellular Mechanisms
Chemotherapy works primarily by targeting rapidly dividing cells, a hallmark of cancer. These drugs interfere with cell division, leading to cell death. This is achieved through various mechanisms, such as damaging DNA, inhibiting cell division, or disrupting cellular metabolism1 5. For instance, drugs like paclitaxel stabilize microtubules, preventing cell division, while others like cisplatin cause DNA crosslinking, leading to apoptosis4.
Tumor Microenvironment
The tumor microenvironment plays a crucial role in the response to chemotherapy. The immune system, in particular, is a significant determinant of chemotherapy efficacy. Chemotherapy can modulate the immune response, either by enhancing antitumor immunity or by creating an immunosuppressive environment. For example, chemotherapy can increase the expression of immune checkpoint molecules like PD-L1, which can suppress T-cell function and promote tumor survival4 5.
Combination Therapies: Enhancing Efficacy
Combination Chemotherapy
Combining different chemotherapeutic agents can enhance treatment efficacy by targeting multiple pathways simultaneously. This approach has been successful in treating various cancers, including Hodgkin's disease, non-Hodgkin's lymphoma, and pediatric solid tumors1. The principles of combination chemotherapy, such as dose scheduling and sequencing, are critical for maximizing therapeutic outcomes1.
Chemo-Immunotherapy
Recent advances have highlighted the potential of combining chemotherapy with immunotherapy. This approach aims to boost the immune system's ability to fight cancer while directly targeting cancer cells with chemotherapy. Studies have shown that certain chemotherapeutic agents can stimulate antitumor immunity, making them effective partners for immune checkpoint inhibitors7 10. For example, combining paclitaxel with PD-L1 inhibitors has shown promising results in ovarian cancer4.
Neoadjuvant and Adjuvant Chemotherapy
Neoadjuvant chemotherapy, administered before surgery, can shrink tumors and reduce the risk of metastasis. This approach has been shown to improve disease-free survival in rectal cancer patients3. Adjuvant chemotherapy, given after primary treatment, aims to eliminate residual microscopic disease, thereby increasing the cure rate and prolonging survival in cancers like breast cancer and osteogenic sarcoma1.
Challenges and Future Directions
Drug Resistance and Side Effects
One of the major challenges in chemotherapy is the development of drug resistance. Tumor cells can adapt to chemotherapeutic agents, rendering them less effective over time. Additionally, chemotherapy can cause significant side effects due to its impact on normal, rapidly dividing cells, such as those in the bone marrow and gastrointestinal tract2 9.
Innovative Strategies
To overcome these challenges, researchers are exploring novel strategies such as metronomic chemotherapy, which involves the frequent administration of low-dose chemotherapeutic agents to minimize toxicity and target the tumor vasculature10. Another promising approach is supramolecular chemotherapy, which uses host-guest molecular recognition to improve drug delivery and reduce side effects9.
Conclusion
Chemotherapy remains a vital tool in the fight against cancer, with its mechanisms of action targeting both cancer cells and the tumor microenvironment. Advances in combination therapies, including chemo-immunotherapy and innovative drug delivery systems, hold promise for improving treatment outcomes and reducing side effects. As research continues, the integration of chemotherapy with other treatment modalities will likely enhance its efficacy and expand its role in cancer care.
Sources and full results
Most relevant research papers on this topic
Curative cancer chemotherapy.
Cancer chemotherapy provides curative treatment for 12 cancer categories, with new treatment strategies like neoadjuvant chemotherapy and autologous bone marrow transplantation promising further improvements.
Highly CitedWhat is cancer chemotherapy?
Cancer chemotherapy is an important treatment modality in oncology, with potential for improvement and development in the near future.
Highly CitedNeoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial.
Neoadjuvant chemotherapy with FOLFIRINOX before preoperative chemoradiotherapy may reduce the risk of distant recurrences in patients with locally advanced rectal cancer.
RCT
Large Human Trial
Rigorous JournalHighly CitedChemotherapy Induces Programmed Cell Death-Ligand 1 Overexpression via the Nuclear Factor-κB to Foster an Immunosuppressive Tumor Microenvironment in Ovarian Cancer.
Chemotherapy in ovarian cancer induces local immune suppression through NF-B-mediated PD-L1 upregulation, suggesting a potential combination of chemotherapy and immunotherapy targeting the PD-L1/PD-1 signaling axis for improved antitumor response.
Non-RCT
Animal StudyHighly CitedCancer chemotherapy: insights into cellular and tumor microenvironmental mechanisms of action
Chemotherapy sensitivity in cancer patients is driven by cellular and tumor microenvironmental factors, with the immune system being a critical determinant.
Literature ReviewHighly CitedA history of cancer chemotherapy.
Cancer chemotherapy has evolved from early 20th-century efforts to screen chemicals in rodents to modern targeted treatments, with molecular abnormalities playing a key role in drug discovery and treatment development.
Highly CitedChemo-Immunotherapy: A New Trend in Cancer Treatment
Chemo-immunotherapy, combining traditional chemotherapy with immunotherapy, shows promising results in treating various types of cancer, but optimal dosing, timing, and sequencing require further investigation.
Literature ReviewChemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial.
Preoperative chemotherapy and postoperative chemoradiotherapy both improve survival in patients with resectable gastric cancer, but perioperative chemotherapy may be more effective for certain subtypes.
RCT
Very Rigorous JournalHighly CitedSupramolecular chemotherapy based on host-guest molecular recognition: a novel strategy in the battle against cancer with a bright future.
Supramolecular chemotherapy based on host-guest recognition shows promise in improving cancer treatment efficacy and reducing side effects by addressing limitations in traditional chemotherapy.
Literature ReviewHighly CitedMetronomic chemotherapy and immunotherapy in cancer treatment.
Metronomic chemotherapy and immunotherapy may improve cancer treatment outcomes by combining their anti-tumor effects and overcoming drug resistance.
Highly Cited