Clinical Applications of Liquid Biopsy in Colorectal Cancer Screening: Current Challenges and Future Perspectives.

Colorectal cancer (CRC) represents the third most prevalent cancer worldwide and a leading cause of mortality among the population of western countries. However, CRC is frequently a preventable malignancy due to various screening tests being available. While failing to obtain real-time data, current screening methods (either endoscopic or stool-based tests) also require disagreeable preparation protocols and tissue sampling through invasive procedures, rendering adherence to CRC screening programs suboptimal. In this context, the necessity for novel, less invasive biomarkers able to identify and assess cancer at an early stage is evident. Liquid biopsy comes as a promising minimally invasive diagnostic tool, able to provide comprehensive information on tumor heterogeneity and dynamics during carcinogenesis. This review focuses on the potential use of circulating tumor cells (CTCs), circulating nucleic acids (CNAs) and extracellular vesicles as emerging liquid biopsy markers with clinical application in the setting of CRC screening. The review also examines the opportunity to implement liquid biopsy analysis during everyday practice and provides highlights on clinical trials researching blood tests designed for early cancer diagnosis. Additionally, the review explores potential applications of liquid biopsies in the era of immunotherapy.

Trifluridine/tipiracil as a therapeutic option in real life setting of metastatic colorectal cancer: An efficacy and safety analysis.

Background: In the phase III RECOURSE trial, the orally administered combination trifluridine/tipiracil (FTD/TPI) demonstrated a survival benefit and an acceptable safety profile, earning approval as a third-line therapy in metastatic colorectal cancer (mCRC). This study aimed to assess the efficacy and safety of FTD/TPI in daily clinical practice in Romanian population. Methods: A single-center, retrospective, and observational study analyzed patients with mCRC that received chemotherapy with trifluridine/tipiracil between May 2019 and May 2022 at the Oncology Institute Prof. Dr. Ion Chiricuța in Cluj-Napoca, Romania. Study endpoints included safety, and median progression-free survival (PFS). Results: In this Romanian cohort (n = 50) the most common treatment-emergent adverse event was haematological toxicity (76%): anemia (50%), leucopenia (38%), neutropenia (34%), and thrombocytopenia (30%), followed by fatigue (60%), and abdominal pain (18%). Overall, the median progression-free survival was 3.85 months (95% CI: 3.1-4.6 months). PFS was significantly correlated with the number of FTD/TPI administrations and prior surgery. Conclusion: Our study corroborated the previously described safety profile for FTD/TPI in the third-line setting, and demonstrated relatively superior mPFS.

Practical Considerations for the Use of Cannabis in Cancer Pain Management-What a Medical Oncologist Should Know.

Pain is a highly debilitating emotional and sensory experience that significantly affects quality of life (QoL). Numerous chronic conditions, including cancer, are associated with chronic pain. In the setting of malignancy, pain can be a consequence of the tumor itself or of life-saving interventions, including surgery, chemotherapy, and radiotherapy. Despite significant pharmacological advances and awareness campaigns, pain remains undertreated in one-third of patients. To date, opioids have been the mainstay of cancer pain management. The problematic side effects and unsatisfactory pain relief of opioids have revived patients' and physicians' interest in finding new solutions, including cannabis and cannabinoids. The medical use of cannabis has been prohibited for decades, and it remains in Schedule 1 of the Misuse of Drugs Regulations. Currently, the legal context for its usage has become more permissive. Various preclinical and observational studies have aimed to prove that cannabinoids could be effective in cancer pain management. However, their clinical utility must be further supported by high-quality clinical trials.

Long Term Administration of Nivolumab for Metastatic Melanoma: A Case Report.

The treatment of metastatic melanoma changed dramatically with the discovery of immune checkpoint inhibitors (ICIs). Patients face prolonged exposure to these agents, which can frequently generate a large spectrum of adverse reactions. It has been shown that a considerable number of patients treated with ICIs achieve a durable response to treatment that is maintained even after cessation. We present the case of a 75-year-old man with metastatic melanoma who underwent 95 cycles of nivolumab without significant treatment-related toxicities or progression. Future studies are needed to define more clearly the optimal duration of anti-programmed cell death protein 1 (PD-1) agents in patients with good tolerance and no progression. Patients could avoid discomfort caused by frequent physician visits, high additional costs, and possible adverse reactions that may occur after such a long period of exposure to immunotherapy.

Landscape of Immunotherapy Options for Colorectal Cancer: Current Knowledge and Future Perspectives beyond Immune Checkpoint Blockade.

Colorectal cancer is the third most prevalent malignancy in Western countries and a major cause of death despite recent improvements in screening programs and early detection methods. In the last decade, a growing effort has been put into better understanding how the immune system interacts with cancer cells. Even if treatments with immune checkpoint inhibitors (anti-PD1, anti-PD-L1, anti-CTLA4) were proven effective for several cancer types, the benefit for colorectal cancer patients is still limited. However, a subset of patients with deficient mismatch repair (dMMR)/microsatellite-instability-high (MSI-H) metastatic colorectal cancer has been observed to have a prolonged benefit to immune checkpoint inhibitors. As a result, pembrolizumab and nivolumab +/- ipilimumab recently obtained the Food and Drug Administration approval. This review aims to highlight the body of knowledge on immunotherapy in the colorectal cancer setting, discussing the potential mechanisms of resistance and future strategies to extend its use.

A Comprehensive Review of the Use of Antioxidants and Natural Products in Cancer Patients Receiving Anticancer Therapy.

Cancer is the leading cause of mortality and morbidity worldwide. The side effects of cancer treatment affect the quality of life. Cancer patients search for antioxidant dietary supplements and natural products during or after conventional cancer treatment for the alleviation of side effects, improvement of the benefits of treatment, and promotion of well-being. However, the efficacy and safety of these products remain controversial; moreover, previous data do not support the standardized use of those alternative treatments in clinics. The current study reviewed the manuscripts reporting the administration of antioxidants and natural products during cancer treatment and revised preclinical and clinical studies on various types of cancer. Most of the positive results were obtained from experimental animal models; however, human clinical studies are discouraging in this regard. Therefore, further precise and distinguishable studies are required regarding antioxidant dietary supplementation. Future studies are also needed to clarify dietary supplements' mechanism of action and pharmacokinetics in a suitable cancer patient population that will benefit the therapeutic regimens. Despite the popularity of dietary supplements, clinicians and patients should always consider their potential benefits and risks. Patients should discuss with their physician before taking any dietary antioxidant supplements or natural products.

A Critical Review of Second-Generation Anti-EGFR Monoclonal Antibodies in Metastatic Colorectal Cancer.

BACKGROUND: Anti-EGFR monoclonal antibodies (mAbs) have become a relevant solution for the treatment of patients with metastatic colorectal cancer. Current anti-EGFR monoclonal antibodies face a series of problems, including resistance and non-durable response, and RAS and BRAF mutations serve as exclusion criteria for treatment with anti-EGFR mAbs. Advances in molecular tumor profiling and information on subsequent pathways responsible for disease progression and drug resistance helped develop a new generation of anti-EGFR mAbs. These second-generation mAbs have been developed to overcome existing resistance mechanisms and to limit common side effects. For the moment, existing literature suggests that these novel anti-EGFR mAbs are far from finding their way to clinical practice soon. OBJECTIVE: In this review, we summarize and evaluate current data regarding ongoing research and completed clinical trials for different second-generation anti-EGFR monoclonal antibodies. CONCLUSION: Anti-EGFR mAbs exhibit efficacy in advanced colorectal cancer, but second-generation mAbs failed to prove their benefit in the treatment of metastatic colorectal cancer. Understanding the biological basis of primary and acquired drug resistance could allow scientists to design better clinical trials and develop improved second-generation mAbs.