Moaven, Omeed

Selective oncotropism and cytolytic activity against tumors have made certain viruses subject to investigation as novel treatment modalities. However, monotherapy with oncolytic viruses (OVs) has shown limited success and modest clinical benefit. The capacity to genetically engineer OVs makes them a desirable platform to design complementary treatment modalities to overcome the existing treatment options' shortcomings. In recent years, our knowledge of interactions of the tumors with the immune system has expanded profoundly. There is a growing body of literature supporting immunomodulatory roles for OVs. The concept of bioengineering these platforms to induce the desired immune response and complement the current immunotherapeutic modalities to make immune-resistant tumors responsive to immunotherapy is under investigation in preclinical and early clinical trials. This review provides an overview of attempts to optimize oncolytic virotherapy as essential components of the multimodality anticancer therapeutic approach and discusses the challenges in translation to clinical practice.

The genetic and molecular underpinnings of metastatic colorectal cancer have been studied for decades, and the applicability of these findings in clinical decision making continues to evolve. Advancements in translating molecular studies have provided a basis for tailoring chemotherapeutic regimens in metastatic colorectal cancer (mCRC) treatment, which have informed multiple practice guidelines. Various genetic and molecular pathways have been identified as clinically significant in the pathogenesis of metastatic colorectal cancer. These include rat sarcoma (RAS), epithelial growth factor receptor (EGFR), vascular endothelial growth factor VEGF, microsatellite instability, mismatch repair, and v-raf murine sarcoma viral oncogene homolog b1 (BRAF) with established clinical implications. RAS mutations and deficiencies in the mismatch repair pathway guide decisions regarding the administration of anti-EGFR-based therapies and immunotherapy, respectively. Furthermore, there are several emerging pathways and therapeutic modalities that have not entered mainstream use in mCRC treatment and are ripe for further investigation. The well-established data in the arena of targeted therapies provide evidence-based support for the use or avoidance of various therapeutic regimens in mCRC treatment, while the emerging pathways and platforms offer a glimpse into the future of transforming a precision approach into a personalized treatment.