In recent years, a new generation of anticancer drugs has emerged, namely targeted anticancer therapy. Chemotherapy, targeted therapies, surgery and radiation therapy have been the mainstay of cancer treatment for many years, but chemotherapy must give way to the next generation: immunotherapy, in which CAR-T cell therapy plays a major role. Like conventional chemotherapy, targeted cancer therapy uses pharmacological agents that inhibit growth, increase cell death, and limit the spread of cancer. Targeted therapy helps block certain proteins in cancer cells that help them grow, divide and spread, while immunotherapy stimulates or suppresses the body’s immune system to fight cancer.
CAR T cell therapy works by taking T cells (a type of immune system cell) from the patient’s blood, inserting the CAR gene (a special receptor that binds to a specific protein on the patient’s cancer cells) into the T cells so that they produce CAR T cells by growing a large number of these new CAR T cells in the lab and introducing these genetically modified cells, which can now recognize and attack cancer cells in a patient. In adoptive cell therapy, immune cells are taken from a patient, modified in a lab to better attack cancer cells, grown in bulk, and injected back into the patient’s body. Immunotherapy helps our immune system fight cancer with a variety of treatments such as monoclonal antibodies, immune checkpoint inhibitors, and adoptive cell therapy.
ACT is a thriving immunotherapy approach that involves harvesting and using patients’ immune cells to treat cancer. Precision oncology has spurred a number of new oncology clinical trials that use NGS to identify genetic vulnerabilities in cancer patients, providing insight into treatment options. Tumors leave traces of their presence in the human body by clearing circulating cancer cells (CTCs), circulating tumor DNA (ctDNA) and ctRNAs, and tiny vesicles called exosomes in the bloodstream. When standard cancer treatments don’t work, or if doctors can’t determine where a patient’s cancer came from, genomic sequencing can help pinpoint mutations in a tumor that could be combined with the drugs they target.
Next generation sequencing has opened the door to personalized cancer treatments by identifying gene mutations in cancer that offer pathways for drug therapy, but this data is not readily available to physicians in a stream of patient records. According to a study published in Gynecologic Oncology, integrating next generation sequencing (NGS) into clinical workflows has proven feasible and has provided information that can help guide treatment decisions for patients with uterine cancer. The aim of this study was to evaluate the clinical usefulness of NGS for therapeutic decision making in a real-life cohort of patients with unknown primary cancer. Significance While gene expression profiling and gene alteration profiling by next generation sequencing (NGS) might be expected to predict primary tumor site and guide targeted therapies at the molecular level to improve clinical outcomes in unknown primary site cancers (CUP), to our knowledge, no a clinical trial has previously evaluated this approach.
Significance. Site-specific treatment, including targeted targeted therapy based on next generation sequencing, is a promising strategy for patients with cancer of unknown primary site and deserves further study in a randomized clinical trial. Results This non-randomized Phase 2 clinical trial of this topical treatment in 97 patients with cancer of unknown primary site and 97 patients with cancer of unknown primary site showed a 1-year survival rate of 53.1% with sustained response to targeted therapy. therapy is observed in patients with viable genetic changes.
Clinical trials evaluating the gene expression profile of individuals diagnosed with CUP to predict tumor origin have shown no difference in PFS or overall survival between topical therapy and empiric chemotherapy. respond poorly to therapy. Of 130 patients treated with sequencing-targeted therapy, nearly 40% experienced some clinical benefit, and 20% had an exceptionally good response, defined as maintaining disease control for at least a year. Of the 83 treated patients, 73 received personalized precision therapy consisting of >= 1 matched molecular treatment; since no two identical molecular profiles existed, most treatment regimens were not exactly the same. Patients were assessed for response every 8 weeks after starting treatment until tumor progression was detected or treatment was completed and all were assessed for survival.
The French SHIVA study compared molecular-targeted therapy based on the molecular profile of the tumor with physician-chosen treatment in patients with various types of metastatic cancer who had failed standard treatment []. In this Dutch study, patients with all types of metastatic cancer were offered the opportunity to undergo a new tumor biopsy for whole genome sequencing (WGS) before starting systemic cancer treatment. In 2012, French researchers launched the SHIVA study, a randomized trial designed to measure whether off-label targeted anticancer drugs can prolong progression-free survival (the length of time after treatment before the cancer worsens). The hope is to start clinical trials here in Ottawa and offer this option to patients with certain types of cancer over the next few years.
While these advances are very real and exciting, more research is needed before immunotherapy is available to cancer patients. Over the past 20 years there has been a wave of innovation in cancer treatment. And, important for evaluating the success of clinical trials, pharmacodynamic biomarkers indicate the effect of treatment. In addition to the discovery of biomarkers, NGS is ushering in an era of precision oncology, a paradigm shift in cancer treatment that aims to match tumor molecular characteristics with targeted drugs to improve patient outcomes.
Biological targets should accurately predict tumor response and/or recurrence risk associated with subgroups of cancer patients that exhibit similar changes. Prognostic biomarkers predict the natural history of untreated cancer (ie, aggressive or less aggressive phenotypes stratified by tumor), while prognostic biomarkers predict patient response to therapy. NGS technology has been successfully used to identify novel mutations in various cancers, such as chronic lymphocytic leukemia, renal cell carcinoma, lung, breast, and colorectal cancer. The Molecular Screening for Cancer Therapy Optimization (MOSCATO 01) study is a prospective, non-randomized study evaluating the clinical benefit of high-throughput genomic profiling in several advanced cancers (n = 1035).