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Conventional cancer therapies have long been focused on eradicating cancer using highest attainable doses of radiation and chemotherapy (maximum tolerated doses or MTD), and radical surgeries. Unless upfront eradication can be achieved, these intensive and toxic therapies are not only ineffective, they can lead to serious complications and poor quality of life.
Targeted therapies combined with repetitive, low-doses of chemotherapy are changing the game in cancer care by allowing for personalized care. This approach allows inhibiting not only the cancer cell, but also modifying the cancer environment. Tufts Medical Center and Floating Hospital for Children, located in downtown Boston, are leading the way in this approach.
As more and more genetic and biologic information becomes available the model of cancer as sequential accumulation of mutations has been replaced by eco-evolutionary theory that recognizes the multiplicity of cancer clones contained in the tumor and their ability to modify tumor microenvironment. The Precision Medicine and Cancer Program team at Tufts Medical Center and Floating Hospital for Children use ‘omics’ in a systems approach to create individualized treatment plans based specifically on the tissue markers found in your tumor. Unlike the traditional approach of focusing treatment based on where the tumor has been found (breast, lung or prostate), this approach focuses the therapy on targeting the patient-specific molecular signature identified by ‘omics’.
We tailor your treatment plan using drugs that specifically target your unique cancer, and pair these drugs with low continuous doses of chemotherapy (also called metronomic chemotherapy).
The aim of low-dose chemotherapy is to create a gradual, sustained tumor-hostile environment that prevents disease progression rather than having an instant impact on tumor size. This approach is successful because it addresses the fact that cancer is not a disease of a single malignant clone, but rather a tumor-induced ecosystem. This finding is often referred to as the eco-evolution of cancer resistance.
If you are a candidate for precision medicine, the team at Tufts MC and Floating Hospital in Boston will take a sample of your tumor tissue and perform an ‘omics’ analysis (genomics, transcriptomics and proteomics) to identify specific genomic alterations that affect tumor growth.
We then do a pathway analysis for each of the gene/protein alterations that were identified. This molecular pathway analysis helps us understand tumor progression by identifying how your genes/proteins interact with each other and generate signals that either activate or inhibit the growth of cancer cells.
Once we have a good sense for your unique cancer and its’ progression, we can choose precisely targeted drugs to inhibit the growth and avoid the spread of your cancer. Because the combination of targeted therapies and high dose chemotherapy further increases the toxicities (targeted therapies sensitize to chemotherapy), we combine targeted therapies with the low-dose continuous chemotherapy and modify the microenvironment of the tumor to drive controlled cancer regression over time.
Targeted therapy uses drugs or other substances that attack targets on cancer cells and cause much less harm to normal cells. The Precision Medicine and Cancer Program team at Tufts MC and Floating Hospital carefully chooses therapies that inhibit/activate specific molecular pathways in your tumor. Because the damage is limited to the tumor tissue, targeted therapies may have fewer side effects than other cancer treatments, but they are not without side effects entirely.
The most common types of targeted therapies are small molecule drugs, monoclonal antibodies and vaccines:
The field of precision medicine has advanced incredibly since April 2000, when those on our team first published their finding that, when used in combination, direct anti-angiogenic and metronomic therapies can inhibit cancer without developing resistant clones or traditional toxicity.
Since 2011, our team has been using genomic signatures to design therapies for children with brain tumors, multiply recurrent cancers, or children with cancers so rare that no standard therapeutic options exist. They have found that even though these cancers may not be fully cured, many of these children are able to return to school and normal activity (in the past they would be in hospice) because these therapies carry less toxicity than traditional approaches.
In January 2016, the precision medicine movement got a huge boost from the creation of the Moonshot 2020 initiative, of which Tufts Medical Center and Floating Hospital for Children are members. This initiative has already gathered pediatric and adult oncologists a number of times to work together and share strategies for improving cancer care. Some of the strategies this group is focusing on for the future are:
We believe that the future of cancer care is in creating a situation in which a person may live with cancer, but not with the disease.