Title : Personalized and precision oncology via integrating genomics, pathology-related modeling, and IT-assisted approaches to prevent, treat, and cure cancer and its complications
Abstract:
Individualizing patient treatment is a core objective of the medical field. Meanwhile, the inherent variability of cancer illustrating the molecular differences between tumors, securing the linkages of those differences to an effective drug and resulting in immense patient benefits, lends itself to the growing field of PPM. Personalized cancer treatment in particular stands to highly benefit from PPM therapies, since extensive variability between tumors presents a need to target each case in a personalized manner.
At this point, personalized cancer therapy is considered to be a treatment strategy centered on the ability to predict which patients are more likely to respond to specific cancer therapies. This approach is founded upon the idea that cancer biomarkers are associated with patient prognosis and tumor response to therapy. And personalized tumor molecular profiles (tumor biomarkers can be OMICS-profiles that predict therapy response.), tumor disease site and other patient characteristics are then potentially used for determining optimum individualized therapy options.
Recent advances in systems biology and cancer pathology have tremendously affected the practice of pathology, gradually transforming it from a morphology-based into a precise molecular-based cancer-related discipline. The improvement of methodology for genomic testing has made it one of the cornerstones of PPM-related cancer medicine (PPO). Various genomic analyses of human cancers are being incorporated into diagnostic and decision-making algorithms of the precision cancer pathology.
In this context, most of advances in PPM-guided cancer management are associated with patient care and treatment, including development of new or more precise individual therapies and genome-driven diagnostics, which had implicated in better outcomes and extended survivals, mostly due to personalized approaches for each tumor, cancer patient and pre-cancer person-at-risk into the PPM era. In order to be effective and successful, PPM-guided approach as applicable to clinical oncology practice assumes the integration of several areas of interdisciplinary knowledge and advanced technologies focused on patient’s characteristics and specific healthy needs, including OMICS sciences, bioinformatics, biomarkers, digital health, data science & sharing, and data bioanalytics. In this context, the implementation of translational studies based on liquid biopsy and organoids or xenografts to evaluate molecular changes due to clonal pressure generated due to the use of target agents or tumor heterogeneity would help in the detection of mechanisms of resistance, suggesting the possibility for novel combinations. Precision pathology has therefore become fundamental not only to inform on tumor diagnosis and prognosis but also to drive therapeutic decisions in daily practice.
Providing functional PPM to cancer patients in real life is very challenging. Biodesign-driven translational research has revolutionized how we develop new treatments for cancer patients. This shift in perspective, in which attention is focused on the specific molecular alterations of the tumor, has opened the door to personalized treatment. This situation is reflected in the increasing number of basket trials selecting specific molecular targets. But the complexity of cancer cells enriched with concomitant molecular alterations complicates identification of the driver. Moreover, tumor heterogeneity could be responsible for the lack of benefit when targeted agents are used. And thus the fusion of the above-mentioned strategies has created a new dimension for PPM-guided cancer therapy. This entails the development of next generation cancer targeted drugs (for therapeutic applications) and individualized cancer vaccines (for preventive purposes). The latter is becoming crucial for personalized & precision cancer therapy since the molecular heterogeneity of cancer, and the complex interaction of cancer, tumor microenvironment and immune cells, require sophisticated combinatorial genotypic and phenotypic testing in order to answer a broad scope of important questions for new cancer-related targeted agent discovery, preclinical and clinical development. So, PPM calls for a transdisciplinary approach, and considerations for how best to develop innovation frameworks to support safe and effective deployment of the new enabling diagnostic and therapeutic technologies in clinical oncology!
