- Collaborations Develop
- Diagnostic and Therapeutic Advances in Pediatric Oncology
- Top 5 Cancers: Therapeutic Advances
- Clinical Cancer Advances 12222 at a Glance
Additionally, at least one antibody drug conjugate, inotuzumab ozogamicin Besponsa , was approved to treat adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia. These inhibitors are especially effective against cancer cells exhibiting gene mutations that are critical in the process of homologous recombination, a process that is crucial for repairing double-stranded DNA breaks.
Olaparib and rucaparib are used in patients with BRCA- mutated ovarian cancer who have received prior chemotherapy. Niraparib is used as a maintenance therapy for patients with platinum-sensitive recurrent ovarian cancer who are in response to platinum-based chemotherapy, regardless of BRCA or tumor homologous recombination status. At least one clinical trial has shown that olaparib was beneficial against breast cancer and more breast cancer trials are underway. The year was noteworthy for the implementation of major new initiatives to fight cancer.
The trial has been accruing between and patients every week and is available at sites. The trial is open to adults with solid tumors including rare tumors , lymphoma, and tumors that no longer respond to standard treatment. The Beau Biden Cancer Moonshot was established to accelerate cancer research and make effective treatments available to more cancer patients in addition to improving prevention and detection methods.
Major goals include encouraging more extensive cooperation and collaboration between researchers in academia, government and the private sector. The specific collaborative and cooperative goals include establishing a national network of patient biological and clinical data, increasing health disparity research, development of biomarkers, technology and preclinical research models and, importantly, methods of data sharing, analytics and predictive computational modeling. The establishment of the NCI Genomic Data Commons GDC , aligned with the Moonshot, will provide all cancer researchers with a unified framework to sharing data, software, expertise, and communications.
The goal is to create the first U. Two recent studies described two different methods for specifically targeting and killing cancer cells. Researchers showed that these tiny nanomachines could instigate the movement of chemical substances into and out of live cells or directly induce cell death. The motor was created in several sizes and could carry peptides designed to target and kill specific cancer cells. The nanomachines were tested in cell-based systems but they have yet to be tested in larger organisms.
The nanorobots carried thrombin to tumor-related vessels resulting in intravascular thrombosis, which caused tumor necrosis and reduced tumor growth. Thrombin is a serine protease that causes the clotting of blood by converting fibrinogen into fibrin. Notably, the nanorobots effectively targeted tumor cells and not normal healthy cells.
Blocking blood vessel growth has many advantages, including applicability to many types of solid tumors and decreased risk of developing resistance. This is the first report showing that nanometer-sized robots successfully delivered drugs to specific places to treat tumors in mammals. Each nanorobot was comprised of fragments of DNA arranged in sheets and four molecules of thrombin were attached to the surface. Thombin can reduce or prevent blood flow to the tumor by forming clots in vessels that feed the tumor.
Each sheet was folded into a hollow tube shape to encase the thrombin protecting it from degradation and preventing its interaction with healthy cells. The nanobots were injected intravenously into mice where they traveled through the bloodstream to the tumor site. The nanobots were programmed to attach only to cancer cells by including a DNA aptamer i.
In this case the DNA aptamer directly targeted nucleolin, which is specifically found on tumor-associated endothelial cells. Within 2 days the nanobots had successfully attached to tumor vessels, causing clots and inhibiting blood supply, resulting in tumor cell death.
Diagnostic and Therapeutic Advances in Pediatric Oncology
Notably, the nanobots only touched tumor cells and had no effect on normal cells. The nanobots have been tested in breast, melanoma, ovarian, and lung cancer mouse models and the hope is to move the technology into humans. Obviously, this is potentially a major breakthrough for cancer treatment if it can be effectively translated into humans.
Many anticancer therapies induce cancer cell death through a process called apoptosis, which requires the activation of proteins called caspases. Apoptosis is usually initiated by disruption of the mitochondrial membrane potential, which results in mitochondrial outer membrane permeabilization MOMP. The process of apoptosis does not always kill all cancer cells, which can lead to recurrence and sometimes results in increased cancer progression. A new and promising area of research involves a process referred to as caspase-independent cell death CICD in which cells die following MOMP even in the absence of caspase activity.
This work was recently published in Nature Cell Biology. The BH3 mimetic functions by binding to multiple members of the anti-apoptotic Bcl-2 protein family to inhibit their activity and restore apoptotic processes in cancer cells. Investigators observed that ABT treatment caused cell death whether or not caspases were active. Investigators determined that necroptosis, a programmed form of necrosis or inflammatory cell death, was likely engaged as a form of CICD.
Top 5 Cancers: Therapeutic Advances
Studies in mouse models revealed that engaging CICD in tumors resulted in inflammatory and immune effects and, notably, almost complete tumor regression. The University of Pennsylvania had received permission from a federal panel to pursue the first trials in the U. Basically, the study will convert normal human immune cells into cancer cell killers and University of Pennsylvania officials hope that the trial can start very soon in early Additional trials are planned in Europe at a later time.
In this trial, immune cells from a patient with lung cancer were used and only PD-1 was disabled before cells were returned to the patient. Secondary outcome measures will include percentage of patients achieving complete response, overall survival, duration of remission, progression-free survival and cause of death when appropriate. Two new strategies were developed that could potentially lengthen life for people with GBM.
The first strategy involves a novel technology known as tumor-treating fields TTFs. TTFs are low-intensity electrical fields believed to be able to put the brakes on cancer growth by blocking cell division. The device was approved for use in combination with temozolomide i. The second major advance against GBM was the discovery that adding temozolomide chemotherapy to short-course radiotherapy resulted in longer survival than radiotherapy alone in elderly patients with GBM.
A proof-of-concept study used a beta version of Watson for Genomics technology to assist in the interpretation of whole-genome sequencing data from a sample of GBM from one patient. The WGA is an automated system that prioritizes somatic variants and identifies drug candidates.
Thus, combining WGA with manual analysis could effectively assist physicians in identifying potential therapies from WGS in less time for more patients. Research has shown that tumor-derived changes in DNA can be detected as cell-free DNA cfDNA in plasma from cancer patients 23 and are generally not found in normal subjects.
Clinical Cancer Advances 12222 at a Glance
Technology is being developed that will allow more sensitive and specific sequencing of cfDNA from plasma. This technique of sequencing cfDNA is referred to as a liquid biopsy and could have several advantages over tumor sequencing. Tumor biopsies are quite invasive and are not very repeatable in patients, whereas the liquid biopsy requires only a blood sample that can be repeated more than once.
Liquid biopsies have the potential to efficiently monitor treatment response and might be used as an early-stage detection tool. Precision oncology now encompasses precision immunotherapies, precision informatics, precisely targeted therapies, and specific cellular engineering all based on next-generation sequencing and genomic profiling. Emerging clinical cancer treatments are progressively and increasingly combining different and varied targeted therapies and pairing those therapies with traditional therapies like chemotherapy and radiation to address the many faces of cancer.
Routine genomic profiling will become more affordable and many believe that it will improve diagnosis and prognosis for the cancer patient. The hope is that genetically-driven tumor dependencies and weaknesses will lead to effective precision combination therapies. However, one of the greatest challenges in genetic profiling is the interpretation of the results. In addition, many of the changes observed might be the result of therapeutic treatment that can result in the activation of off-target pathways to bypass the intended targeted pathway.
How will resistance be addressed, which occurs almost universally with targeted cancer therapies? Resistance is a complex issue that can involve reactivation of the targeted pathway through additional genomic mutations either in the targeted gene or another, which can result in bypass of the intended target and tumor growth. This knowledge has led to multi-drug therapies to maintain efficacy. What are the variables that are most important for the successful implementation of precision oncology in the clinic?
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Clearly, we must identify proven, validated therapeutic targets and develop drugs that directly interact with those targets resulting in their deactivation and elimination. We must understand the mechanisms underlying resistance. Perhaps, techniques such as liquid biopsies could be key in understanding resistance based on cfDNA samples obtained from the tumor before treatment, throughout treatment, and after treatment. Precision oncology clearly comprises more than just genomic profiling. These insidious multifaceted diseases are capable of continually adapting to and interacting with a harsh microenvironment, which we do not totally understand, to survive and even thrive.
Anti-cancer drugs are being rapidly developed, tested and approved by the FDA in an expedited effort to get the drugs to as many patients as possible in the shortest and safest timeframe. Combinations of therapeutics to attack multiple cancer signaling pathways are rapidly being seen as more effective than a single drug treatment because of eventual acquired resistance.
Immunotherapies have made a significant and positive impact on survival and quality of life in some patients. Even so, resistance is also an issue with these therapies. However, practically speaking, one institution or one agency cannot be solely responsible for every aspect of comprehending the complexities of cancer. The realization of effective and efficient precision oncology will not work if institutions do not talk with each other.
Understanding these diseases and how to treat them precisely will absolutely require a tremendous collaborative and integrative effort between research and medical institutions worldwide. Bode, A. Precision oncology- the future of personalized cancer medicine?. Long, G. Yates, L. Gross, S.