Colorectal cancer (CRC) is the third most common malignancy worldwide. Surgery remains the most important treatment for non-metastatic CRC, and the administration of adjuvant chemotherapy depends mainly on the disease stage, which is still the strongest prognostic factor. A refined understanding of the genomics of CRC has recently been achieved thanks to the widespread use of next generation sequencing with potential future therapeutic implications. Microsatellite instability (MSI) has been suggested as a predictive marker for response to anti-programmed-cell-death protein 1 (PD-1) therapy in solid tumors, including CRC. It should be noted that not all cancers with MSI phenotype respond to anti-PD-1 immunotherapy, highlighting the urgent need for even better predictive biomarkers. Mitogen-Activated Protein Kinase (MAPK) pathway genes KRAS, NRAS, and BRAF represent important molecular targets and could serve as independent prognostic biomarkers in CRC, and identify those who potentially benefit from anti-epidermal growth factor receptor (EGFR) treatment. Emerging evidence has attributed a significant role to inflammatory markers including blood cell ratios in the prognosis and survival of CRC patients; these biomarkers can be easily assessed in routine blood exams and be used to identify high-risk patients or those more likely to benefit from chemotherapy, targeted therapies and potentially immunotherapy. Analysis of cell-free DNA (cfDNA), circulating tumor cells (CTC) and/or micro RNAs (miRNAs) could provide useful information for the early diagnosis of CRC, the identification of minimal residual disease and, the evaluation of the risk of recurrence in early CRC patients. Even the selection of patients suitable for the new targeted therapy is becoming possible with the use of predictive miRNA biomarkers. Finally, the development of treatment resistance with the emergence of chemo-resistance clones after treatment remains the most important challenge in the clinical practice. In this context it is crucial to identify potential biomarkers and therapeutic targets which could lead to development of new and more effective treatments.

Malignant spinal cord compression (MSCC) is one of the most devastating complications of cancer. Patients often present with a history of progressive pain, paralysis, sensory loss, progressive spinal deformity, and loss of sphincter control. It is an emergency that requires rapid decision making on the part of several specialists, given the risk of permanent spinal cord injury or death. The goals of treatment in spinal metastases are pain control and improvement of neurological function in order to achieve better quality of life (QoL). The standard of care in most cases is rapid initiation of corticosteroids in combination with either surgical decompression in case of an operable candidate, followed by radiation therapy (RT) or RT alone. Surgery is associated with improved outcomes, but is not appropriate for many patients presenting with advanced symptoms of MSCC, such as paralysis, or those with a poor performance status, or cachexic state, as well as altered mental conditions, co-morbidities, surgical risks, and limited life expectancy. On the other hand, aggressive surgical treatment and post-operative RT is advocated for those with more favorable prognosis, or who are expected to have higher neurological recovery potential. Many candidates may require for combined anterior and posterior approaches to effectively deal with the compressive pathology and stabilize the spine. Most patients are presently treated by primary RT, given with the aim of improving function and symptom management. However, there is still debate regarding the most appropriate RT schedule. Rehabilitation can serve to relieve symptoms, QoL, enhance functional independence, and prevent further complications. Ambulatory status has been found to be an important prognostic factor for patients with MSCC.

Poly (ADP-ribose) polymerase (PARP) inhibitors are a novel class of therapeutic agents that target tumors with deficiencies in the homologous recombination DNA repair pathway. Genomic instability characterizes high-grade serous ovarian cancer (HGSOC), with one half of all tumors displaying defects in the important DNA repair pathway of homologous recombination. Early studies have shown significant efficacy for PARP inhibitors in patients with germline breast related cancer antigens 1 and 2 (BRCA1/2) mutations. It has also become evident that BRCA wild-type patients with other defects in the homologous recombination repair pathway benefit from this treatment. Companion homologous recombination deficiency (HRD) scores are being developed to guide the selection of patients that are most likely to benefit from PARP inhibition. The choice of which PARP inhibitor is mainly based upon the number of prior therapies and the presence of a BRCA mutation or HRD. The identification of patients most likely to benefit from PARP inhibitor therapy in view of HRD and other biomarker assessments is still challenging. The aim of this review is to describe the current evidence for PARP inhibitors in ovarian cancer, their mechanism of action, and the outstanding issues, including the rate of long-term toxicities and the evolution of resistance.

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