Introduction: Mutant KRAS is a genetic driver of multiple cancers that has challenged clinical anti-cancer therapeutics in the last 3 decades. Neo-antigens encoded by KRAS mutations have been identified as tumor-specific with high immunogenicity and can be used to deliver precision cancer vaccines to promote anti-tumor immune responses. KRAS mutation-based cancer vaccines have produced encouraging preclinical and clinical results. Cancer vaccines represent a promising approach to treat KRAS-driven cancers. Areas covered: In this review, we summarize the development and progress of vaccines targeting KRAS and evaluate their potential benefits and obstacles in the current landscape of therapy for KRAS-driven cancers. Expert opinion: KRAS mutation-based cancer vaccines can induce immunogenicity in patients with KRAS-driven cancers. However, the mechanisms of tumor suppression including cellular and molecular factors within the tumor microenvironment may limit vaccine efficacy. Combining KRAS-driven therapeutic cancer vaccines with other methods and adjuvants can circumvent immunosuppression and promote therapeutic successes.
Male primary choriocarcinoma is a rare and invasive malignant neoplasm for which traditional chemotherapy has limited efficacy. Pembrolizumab is a humanized monoclonal anti-programmed death-1 antibody that has antitumor activity in numerous malignancies. The diagnosis and treatment of two cases of advanced male primary choriocarcinoma were retrospectively analyzed and relevant literature was reviewed to discuss the prognosis and the efficacy of different treatments, including pembrolizumab. The first patient, who presented with cough and hemoptysis, was diagnosed with primary mediastinal choriocarcinoma. He initially responded to the first-line chemotherapy of etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine, but eventually developed brain metastases. The patient did not respond to the second-line chemotherapy comprising paclitaxel and cisplatin, and he died 6.5 months after diagnosis. The second patient experienced repeated episodes of abdominal pain and was diagnosed with primary neck choriocarcinoma. He received chemotherapy regimens similar to those of the first patient. However, imaging showed no significant changes and his clinical symptoms were not improved. Immunohistochemistry showed that the expression of programmed death ligand 1 on the tumor cells was 40%, and he was administered pembrolizumab combined with chemotherapy. He achieved complete response and was subsequently switched to pembrolizumab maintenance monotherapy. He is still alive without evidence of disease 36 months after diagnosis. To our knowledge, this is the first case of advanced male primary choriocarcinoma successfully treated with pembrolizumab combined with chemotherapy. Advanced male primary choriocarcinoma is highly aggressive and insensitive to chemotherapy. Pembrolizumab may provide a promising treatment option to improve patient outcomes.
Pembrolizumab, an immune checkpoint inhibitor against the programmed death‑1 pathway, has been used in combination with acitinib for the first‑line treatment of advanced renal cell carcinoma. Neurotoxicity is a rare immune‑related adverse event (irAE). The present study reports a case of Guillain‑Barre syndrome (GBS) induced by pembrolizumab and sunitinib, and reviews other previous studies to elucidate the clinical characteristics and suitable management of this rare irAE. An advanced renal cell carcinoma patient who received several cycles of pembrolizumab combined with sunitinib developed limb weakness and numbness of the extremities, and was diagnosed with GBS by electrodiagnostic and cerebrospinal fluid examination. The patient improved after treatment with intravenous immunoglobulin along with prednisone. To the best of our knowledge, this is the first case of GBS during treatment with pembrolizumab in combination with sunitinib in advanced renal cell carcinoma.
Radiation-induced lung injury is a significant complication of thoracic malignant tumor radiotherapy, yet effective treatments remain scarce. Aldehyde dehydrogenase 2 (ALDH2) possesses antioxidant and anti-inflammatory properties, but its specific role in radiation-induced lung injury is not well understood. This study aimed to investigate the impact of ALDH2 on radiation-induced lung injury and elucidate the underlying mechanisms. Through analysis of radiation-induced lung injury datasets, intervention with ALDH2 agonists and inhibitors in an in vivo radiation-induced lung injury model, and establishment of an in vitro radiation-induced lung injury model using A549 stable cells with varying ALDH2 expressions, we discovered that ALDH2 expression is reduced in radiation-induced lung injury. Enrichment analysis suggested that ALDH2 may mitigate radiation-induced lung injury by modulating oxidative stress and inflammation levels. Additionally, single-cell data analysis reveals that ALDH2 is primarily localized in myeloid macrophages within the lungs, with its expression also being reduced in lung cancer patients. Subsequent examination of mouse pathological sections, reactive oxygen species (ROS), and inflammatory factor levels confirmed that ALDH2 can lessen radiation-induced lung injury by suppressing ROS and inflammatory factors. Both in vivo and in vitro Western blot analysis further validated that ALDH2 can attenuate epithelial-mesenchymal transition and inhibit the TGF-β1/Smad pathway. Therefore, ALDH2 shows promise in reducing radiation-induced lung injury by inhibiting ROS and TGF-mediated epithelial-mesenchymal transition, making it a potential target for the treatment of radiation-induced lung injury.
Synovial sarcomas commonly occur in the soft tissue of the extremities, while a primary occurrence in the mediastinum is quite rare. The current study reports the case of an 11-year-old male who presented with a neck mass, which computed tomography showed was due to a giant mediastinal mass involving the thyroid gland. The tumor was resected by thoracotomy and diagnosed as monophasic synovial sarcoma by histopathology. The patient received adjuvant combination chemotherapy and radiation therapy following surgery. At the 3-month follow-up, no local tumor recurrence was found. The present case report highlights the significance of recognizing the unusual presentation and clinical manifestation of synovial sarcoma to aid clinical management. Written informed consent was obtained from the patient’s family.