Colorectal cancer (CRC) is one of the most common cancers worldwide, being the third most diagnosed in the world and the second deadliest. Solid biopsy provides an essential guide for the clinical management of patients with colorectal cancer; however, this method presents several limitations, in particular invasiveness, and cannot be used repeatedly. Recently, clinical research directed toward the use of liquid biopsy, as an alternative tool to solid biopsy, showed significant promise in several CRC clinical applications, as (1) detect CRC patients at early stage, (2) make treatment decision, (3) monitor treatment response, (4) predict relapses and metastases, (5) unravel tumor heterogeneity, and (6) detect minimal residual disease. The purpose of this short review is to describe the concept, the characteristics, the genetic components, and the technologies used in liquid biopsy in the context of the management of colorectal cancer, and finally we reviewed gene alterations, recently described in the literature, as promising potential biomarkers that may be specifically used in liquid biopsy tests.

Background: The aim of this study is to report tumoral genetic mutations observed at high sequencing depth in a lung squamous cell carcinoma (SqCC) sample. We describe the findings and differences in genetic mutations that were studied by deep next-generation sequencing methods on the primary tumor and liver metastasis samples. In this report, we also discuss how these differences may be involved in determining the tumor progression leading to the metastasis stage. Methods: We followed one lung SqCC patient who underwent FDG-PET scan imaging, before and after three months of treatment. We sequenced 26 well-known cancer-related genes, at an average of ~6,000 × sequencing coverage, in two spatially distinct regions, one from a primary lung tumor metastasis and the other from a distal liver metastasis, which was present before the treatment. Results: A total of 3,922,196 read pairs were obtained across all two samples' sequenced locations. Merged mapped reads showed several variants, from which we selected 36 with high confidence call. While we found 83% of genetic concordance between the distal metastasis and primary tumor, six variants presented substantial discordance. In the liver metastasis sample, we observed three de novo genetic changes, two on the FGFR3 gene and one on the CDKN2A gene, and the frequency of one variant found on the FGFR2 gene has been increased. Two genetic variants in the HRAS gene, which were present initially in the primary tumor, have been completely lost in the liver tumor. The discordant variants have coding consequences as follows: FGFR3 (c.746C>G, p. Ser249Cys), CDKN2A (c.47_50delTGGC, p. Leu16Profs^*9), and HRAS (c.182A>C, p. Gln61Pro). The pathogenicity prediction scores for the acquired variants, assessed using several databases, reported these variants as pathogenic, with a gain of function for FGFR3 and a loss of function for CDKN2A. The patient follow-up using imaging with 18F-FDG PET/CT before and after four cycles of treatment shows discordant tumor progression in metastatic liver compared to primary lung tumor. Conclusions: Our results report the occurrence of several genetic changes between primary tumor and distant liver metastasis in lung SqCC, among which non-silent mutations may be associated with tumor evolution during metastasis.

Liquid biopsy gained significant interest in the area of cancer management. This study aims to evaluate the effectiveness of molecular testing using ctDNA (circulating tumor DNA) to; detect genetic alterations, screen for abnormalities, identify mutations associated with treatment sensitivity or resistance and guide therapy decision for several types of cancer in patients with metastasis. A total of 85 samples were collected from 74 patients recruited at our center, as part of their routine clinical follow-up. 17 different cancer types were analyzed. Genetic testing was conducted in patients with metastasis after failure of standard treatments. Sequencing was conducted in plasma-ctDNA samples; and when it was possible on the tumor tissue as well. Our analysis revealed that 88% (65 patients) of patients were eligible for treatment guidance using liquid biopsy. Among them, 64% (47 patients) received an FDA-approved drug, and treatment decisions were based on molecular testing using ctDNA. Somatic gene mutations were detected in 89% (66 patients) of the patients tested; 81% (60 patients) of patients had at least two mutations, 8% (6 patients) had only one mutation and 11% (8 patients) had no detected mutations. Interestingly, among the genes tested, BRCA2, EGFR, MSH6, and NF1 were the most frequently mutated in our patients. Our study highlights the potential benefits of personalized medicine through a non-invasive genetic testing across patients with metastasis regardless of the cancer types. Moreover, our study identified the frequent occurrence of specific gene mutations across various types of cancer, which paves the way for considering targeted therapies that could be applicable to multiple cancer types, rather than being restricted to just a few.

Mammography, as of today, is used as a gold standard for screening, diagnosing, and monitoring breast cancer (BC). While overall beneficial, it presents several downsides, such as limitations in accuracy, relatively high costs, and dependence on heavy infrastructure, greatly limiting accessibility for the entire global target population. There is currently no established alternative to mammography, and overcoming this major challenge is a hot topic in research and technology. One avenue for tackling this issue is the development of highly sensitive and specific non-invasive blood tests for the early diagnosis and follow-up of breast cancer. This paper discusses the limitations of mammography and recapitulates the blood tests already available, those under development, and future developments in this field.

Lung cancer (LC) remains the leading cause of cancer-related mortality worldwide, representing a major public health challenge. Although low-dose computed tomography is currently the standard screening method for high-risk individuals to reduce mortality, its clinical performance is limited by false-positive findings and restricted accessibility. Emerging biomarker-based liquid biopsy offers a promising non-invasive approach for cancer detection. This narrative review provides a critical overview and evaluation of clinically endorsed liquid biopsy applications for guiding treatment in advanced-stage lung cancer, as well as investigational advances in liquid biopsy for early cancer detection. We also address challenges of current liquid biopsy technologies, the integration of artificial intelligence, implementation improvements, and future perspectives for their adoption into routine clinical practice. To complement this narrative review, a structured search of the ClinicalTrials.gov registry was performed to identify clinical trials evaluating liquid biopsy in lung cancer. Current evidence supports the clinical use of liquid biopsy for molecular profiling and treatment selection in advanced non-small cell lung cancer (NSCLC), whereas its application in early detection, screening, and minimal residual disease (MRD)-guided management remains investigational and requires further prospective validation. Overall, liquid biopsy represents a promising complementary approach to advance precision oncology and improve lung cancer management.

Poly-ADP-ribose polymerase (PARP) inhibitors represent a novel class of anticancer agents that leverage the principle of synthetic lethality to induce tumor cell death by disrupting defective DNA repair pathways. PARP inhibitors have demonstrated strong preclinical activity in tumors with homologous recombination (HR) repair deficiencies. The discovery of synthetic lethality between HR defects and PARP inhibition led to multiple clinical trials, first in BRCA1/2-mutated cancers and later in other HR-deficient tumors. PARP inhibitors have become essential components of first- and later-line therapies for breast, prostate, pancreatic, and ovarian cancers, with several agents already approved by the FDA. However, their therapeutic potential in other malignancies remains less defined, as limited studies have explored their efficacy in additional solid tumors. This article provides an updated overview of PARP inhibitors use beyond their established clinical indications, highlighting current evidence, combination strategies, and emerging perspectives that may expand their role in various cancer treatment including endometrial cancer, cervical cancer, kidney cancer, colorectal cancer, non–small cell lung cancer (NSCLC), small cell lung cancer (SCLC) and other malignancies.