International Journal of Clinical Case Reports, 2025, Vol.15, No.3, 139-147 http://medscipublisher.com/index.php/ijccr 142 One study showed that bevacizumab helped blood vessels in tumors work more normally. This let chemo reach deeper into the tumor and also brought in more oxygen (Zhen et al., 2019). Another study found that adding immune drugs to chemo helped more immune cells enter the tumor and kill more cancer cells (He et al., 2021). 3.2 Preclinical evidence Animal studies give us more clues about how these drugs work together. In one study, researchers used immune drugs and targeted drugs to treat cervical cancer caused by HPV. The combo made more cancer cells die and made tumors smaller. They also used CRISPR to block HPVE6/E7 genes. When this was combined with a PD-1 drug, tumors shrank more and the immune system worked harder (Zhen et al., 2019). Another study tested a new way to give drugs. They used small particles (nanoparticles) filled with paclitaxel and siRNA. When used with cisplatin, tumor growth was blocked by over 80%. Cisplatin alone only stopped about 50% (Figure 2) (Xu et al., 2020). This shows that using new methods with chemo can make it work better. Fiugre 2 Co-delivery of paclitaxel and siRNA-E7 using a bioinspired tumor-homing nanoplatform to synergistically treat HPV-associated cervical malignancies (Adopted from Xu et al., 2020) 3.3 Role of tumor microenvironment The area around the tumor is called the tumor microenvironment (TME). It plays a big role in how well treatments work. In cervical cancer, the TME often has low oxygen, weak immune cells, and thick tissue. These problems make it hard for drugs to reach the tumor. Bevacizumab can help with this. It makes the tumor’s blood vessels work better. That way, more oxygen and drugs can get in. One study showed that this also let more immune cells enter the tumor. It turned the TME from "cold" (not much immune action) to "hot" (active immune attack) (Yang et al., 2022). Chemo can also affect the TME. When chemo kills cancer cells, the dead cells release signals called antigens. These signals make immune drugs work better. In one study, using cisplatin with a heat-triggered form of interferon-alpha made the body’s immune system fight more strongly. The animals that got this treatment also lived longer (Li et al., 2024). By hitting both the cancer and the area around it, the combo of chemo and targeted drugs can stop the cancer in more ways. It can also stop the cancer from coming back and make the treatment work better overall. 4 Current Clinical Evidence 4.1 Clinical trials Clinical trials say using both targeted drugs and chemo can work better than chemo alone. The GOG-240 trial is a good example. In this study, doctors added bevacizumab (which blocks VEGF) to regular chemo—either cisplatin and paclitaxel or topotecan and paclitaxel. They tried this on people whose cervical cancer came back, spread, or didn’t go away.
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