Postoperative Chemotherapy After Surgical Resection of Metachronous Metastases of Colorectal Cancer: A Systematic Review.

Currently, 6 months of perioperative or adjuvant chemotherapy (ACT) is a standard treatment option after radical surgical removal of metachronous metastases in patients with metastatic colorectal cancer (CRC). Data show that ACT improves relapse-free survival in such patients, although no difference in overall survival rate was observed. We perform a systematic review to evaluate the efficacy of adjuvant chemotherapy after radical resection of metachronous metastases in CRC.

Endocrine therapy for metastatic solid pseudopapillary neoplasm of the pancreas: A case report.

Solid pseudopapillary neoplasm (SPN) of the pancreas is an extremely rare tumor, associated with favorable prognosis and long-term survival in patients with advanced disease. However, limited data exist on systemic therapy for such patients. Herein, we present a case of a young woman with a history of SPN, who progressed after multiple surgical resections and chemotherapy regimens. The immunohistochemistry (IHC) showed overexpression of estrogen receptors (ER) and progesterone receptors (PR) in tumor tissue. The patient started to receive tamoxifen and showed a durable response to endocrine therapy.

Complete response to talazoparib in patient with pancreatic adenocarcinoma harboring somatic PALB2 mutation: A case report and literature review.

PARP inhibitors have recently emerged as a maintenance treatment option for metastatic pancreatic cancer patients with germline BRCA mutations. However, the possibility of PARP-inhibitor use as a standalone-targeted therapy for patients with various homologous repair pathway alterations remains mostly undetermined. Here we report a clinical case of a 56-year-old woman with pancreatic ductal adenocarcinoma harboring a somatic PALB2 mutation. Following disease progression after 10 cycles of FOLFIRINOX chemotherapy and two cycles of second-line gemcitabine, she was switched to talazoparib and achieved a complete clinical response after 25 months of treatment. The patient remains alive without clinical or radiological signs of disease progression three years after the start of talazoparib with no targeted therapy-related toxicities. This case highlights the role of broad molecular profiling as a window of opportunity to achieve a durable response for selected pancreatic cancer patients while pinpointing our gaps in understanding the whole picture of management of these patients since a new puzzle element represented by PARP inhibitors was introduced to clinical practice.

9-ING-41, a Small Molecule Inhibitor of GSK-3ß, Potentiates the Effects of Chemotherapy on Colorectal Cancer Cells.

Colorectal cancer (CRC) is one of the most common and lethal types of cancer. Although researchers have made significant efforts to study the mechanisms underlying CRC drug resistance, our knowledge of this disease is still limited, and novel therapies are in high demand. It is urgent to find new targeted therapy considering limited chemotherapy options. KRAS mutations are the most frequent molecular alterations in CRC. However, there are no approved K-Ras targeted therapies for these tumors yet. GSK-3ß is demonstrated to be a critically important kinase for the survival and proliferation of K-Ras-dependent pancreatic cancer cells. In this study, we tested combinations of standard-of-care therapy and 9-ING-41, a small molecule inhibitor of GSK-3ß, in CRC cell lines and patient-derived tumor organoid models of CRC. We demonstrate that 9-ING-41 inhibits the growth of CRC cells via a distinct from chemotherapy mechanism of action. Although molecular biomarkers of 9-ING-41 efficacy are yet to be identified, the addition of 9-ING-41 to the standard-of-care drugs 5-FU and oxaliplatin could significantly enhance growth inhibition in certain CRC cells. The results of the transcriptomic analysis support our findings of cell cycle arrest and DNA repair deficiency in 9-ING-41-treated CRC cells. Notably, we find substantial similarity in the changes of the transcriptomic profile after inhibition of GSK-3ß and suppression of STK33, another critically important kinase for K-Ras-dependent cells, which could be an interesting point for future research. Overall, the results of this study provide a rationale for the further investigation of GSK-3 inhibitors in combination with standard-of-care treatment of CRC.

Breast cancer organoid model allowed to reveal potentially beneficial combinations of 3,3'-diindolylmethane and chemotherapy drugs.

Epigenetic alterations represent promising therapeutic targets in cancer treatment. Recently it was revealed that small molecules have the potential to act as microRNA silencers. Capacity to bind the discrete stem-looped structure of pre-miR-21 and prevent its maturation opens opportunities to utilize such compounds for the prevention of initiation, progression, and chemoresistance of cancer. Molecular simulations performed earlier identified 3,3'-diindolylmethane (DIM) as a potent microRNA-21 antagonist. However, data on DIM and microRNA-21 interplay is controversial, which may be caused by the limitations of the cell lines.

Bidirectional chemotherapy in gastric cancer with peritoneal metastasis combining intravenous XELOX with intraperitoneal chemotherapy with low-dose cisplatin and Doxorubicin administered as a pressurized aerosol: an open-label, Phase-2 study (PIPAC-GA2).

Background: Peritoneal metastasis (PM) develop in more than 50 % of gastric cancer (GC) patients. Median survival without treatment is not more than 3-7 months, and 8-12 months after modern combination chemotherapy. Innovative therapeutic approaches are urgently needed. Methods: Phase-2, open label prospective clinical trial assessing safety and efficacy of bidirectional chemotherapy for treating peritoneal metastasis of gastric cancer (PMGC). Treatment protocol included initial staging laparoscopy or laparotomy, 3-4 courses of systemic chemotherapy (XELOX) followed by Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) procedures every 6 weeks until progression of disease or death. Primary endpoints were overall survival and histological peritoneal regression grading score after rebiopsy. Results: 31 patients were included (9 men, 22 women, mean age 52 years), 24 with synchronous PM at diagnosis, 7 with metachronous PM after previous chemotherapy. Mean PCI was 13.8 (min-max 6-34). XELOX was administered in all patients and combined with 56 PIPAC procedures. Complete and partial pathological response was found in 60 % of the 15 patients eligible for tumor response assessment (4 and 5 patients, respectively). Median survival was 13 months. Conclusions: Bidirectional chemotherapy combining XELOX with PIPAC with cisplatin and doxororubicin is well tolerated, can induce objective tumor regression and is associated with a promising survival in PMGC.