Chemotherapy is a therapy of choice for many cancers. However, it is often inefficient for long-term patient survival and is usually accompanied by multiple adverse effects. The adverse effects are mainly associated with toxicity to normal cells, frequently resulting in immune system depression, nausea, loss of appetite and metabolic changes. In this respect, the combination of chemotherapy with cannabinoids, especially non-psychoactive, such as cannabidiol, cannabinol and other minor cannabinoids, as well as terpenes, may become very useful. This is especially pertinent because the mechanisms of anticancer effects of cannabinoids on cancer cells are often different from conventional chemotherapeutics. In addition, cannabinoids help alleviate chemotherapy-induced adverse effects, regulate sleep and appetite, and are shown to have analgesic properties. Another component for achieving potential anti-cancer synergism is regulating nutrient availability and metabolism by calorie restriction and intermittent fasting in cancer cells. As tumours require a lot of energy to grow and because glucose is constantly available, malignant cells often opt to use glucose as a primary source of ATP production through substrate-level phosphorylation (fermentation) rather than through oxidative phosphorylation. Thus, periodic depletion of cancer cells of primary fuel, glucose, could result in a strong synergy in killing cancer cells by chemo- and possibly radiotherapy when combined with cannabinoids. This commentary will discuss what is known about such combinatorial treatments, including potential mechanisms and future protocols.
Approximately 20% of lung cancer patients have brain metastasis at diagnosis, which is associated with a worse prognosis and a negative impact on quality of life. The emergence of new systemic treatment options such as immune checkpoint inhibitors (ICI) and targeted therapies changed the prognosis for stage IV lung cancer patients. However, the impact of local and systemic treatment sequencing in patients with stage IV lung cancer and brain metastasis is still unclear. We present the case of a 51-year-old man with stage IV non-small cell lung cancer and brain metastasis at diagnosis who underwent whole brain radiotherapy (WBRT) and achieved intracranial and extracranial complete response after second-line treatment with an ICI. Currently, the patient has an overall survival of 87 months and a progression-free survival of 73 months with an optimal quality of life. We hypothesized that treatment sequencing of WBRT and immunotherapy could explain this unexpected outcome.
Poly (ADP-ribose) polymerases (PARP) inhibitors (PARPi) are the first-approved anticancer drug designed to exploit synthetic lethality. PARPi selectively kill cancer cells with homologous recombination repair deficiency (HRD), as a result, PARPi are widely employed to treated BRCA1/2-mutant ovarian, breast, pancreatic and prostate cancers. Currently, four PARPi including Olaparib, Rucaparib, Niraparib, and Talazoparib have been developed and greatly improved clinical outcomes in cancer patients. However, accumulating evidences suggest that required or de novo resistance emerged. In this review, we discuss the molecular mechanisms leading to PARPi resistances and review the potential strategies to overcome PARPi resistance.
Mesothelioma is an incurable cancer of the mesothelial lining often caused by exposure to asbestos. Asbestos-induced inflammation is a significant contributing factor in the development of mesothelioma, and genetic factors also play a role in the susceptibility to this rapidly progressive and treatment-resistant malignancy. Consequently, novel approaches are urgently needed to treat mesothelioma and prevent or reduce the overall incidence of this fatal disease. In this research perspective, we review the current state of chemoprevention and cancer interception progress in asbestos-induced mesothelioma. We discuss the different preclinical mouse models used for these investigations and the inflammatory factors that may be potential targets for mesothelioma prevention. Preliminary studies with naturally occurring phytochemicals and synthetic agents are reviewed. Results of previous clinical chemoprevention trials in populations exposed to asbestos and considerations regarding future trials are also presented.