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Chemotherapy resistance and failure

Chemotherapy resistance is induced after high dose chemotherapy as cancer adapts to its environment. Circulating cancer cells are cancer cells that have broken away from the primary tumor and have entered the bloodstream and cause metastatic disease. These cancer cells are resistant to chemotherapy; in fact, they are stimulated by chemotherapy. As reported in the New England Journal of Medicine “potential uses of circulating tumor biomarkers,” it was found that the cells can now be demonstrated in the blood of cancer patients and are useful as markers. They are evaluated in each patient.

Recent studies at the Moffitt Cancer Center in Tampa Bay, Florida, demonstrated that low-dose metronomic chemotherapy could keep the tumor burden stable, thus not allowing chemo resistant cells to rise. Also, chemoresistance occurs through different proteins such as MDR or P glycoprotein. These can pump the chemotherapy out of the cancer cell.

These resistance factors can now be evaluated in your blood and reversed before the administration of low-dose chemotherapy. I used both prescription and natural substances to do this. By reversing the resistant pathways, you have a higher success rate in your treatments.

Multidrug resistance caused by the overexpression is a significant obstacle in clinical cancer chemotherapy usage. It appears that by direct inhibition of the ABC transporters, we can restore drug sensitivity to multidrug-resistant cancer cells.

There are many natural substances that are non-toxic and well-tolerated by the human body. Some include natural products such as curcumin and the bioflavonoids that modulate the ABC drug transporters. A recent medical article published in the Current Pharmaceutical Biotechnology entitled "Discovering natural products modulation to overcome multidrug resistance in cancer chemotherapy” found them to restore drug sensitivity and inhibit resistance to chemotherapy. I always employ them when I use low-dose chemotherapy. I used chemotherapy based on genomic molecular testing.

These include genistein, Ginger, garlic, capsaicin, dark chocolate with 70% or higher cocoa, black tea, green tea, and ginkgo. Prescription drugs such as verapamil and ketoconazole will reverse MDR 1 resistance. It is truly exciting the natural substances, in addition to many more, can reverse drug resistance.

Over the last 42 years, I have seen many patients whose cancer has returned. The reason being it had in the past, we have not been able to evaluate the cancer genome. Most chemotherapies are based on either retrospective or clinical studies. Due to the availability of next-generation sequencing, we can now analyze the cancer genome. Now that genome-wide mutational analysis is available, we realize that there are a handful of genes that are mutated in a high fraction of tumors.

In most tumor types, a fraction of a patient’s tumors are refractory to therapies; this is called intrinsic resistance. Even if an initial response to therapies is obtained, most tumors subsequently become refractory during, and this is called acquired resistance. This can cause disease progression. Therefore, this secondary resistance should be regarded as a key obstacle to treatment progress. We need to analyze the cancer genome, and this represents a powerful tool for the identification of chemotherapeutic signatures as well as understanding resistant mechanisms. The good news is these resistant factors can now be tested for and reversed.

Molecular analysis of cancer genomic

By sequencing the drivers of cancer, we can more adequately treat our patients. Cancer genomics has dramatically impacted disease management because the new targeted therapies are all personalized and individualized to each patient. The problem with using single-molecule targeted therapy is that it is almost followed by acquired drug resistance. The new genomic analysis can decipher resistant mechanisms to these inhibitors. As reported in the New England Journal of Medicine, “identification of a molecular target for therapy,” substantial progress has been made in the treatment of specific molecular subsets of lung adenocarcinoma. Treatments can now be personalized. Multimodal therapy is best to present resistance and failure.

Genomic personalized treatment

The completion of the human genome project has changed the landscape of cancer treatment. Through mutational profiling and next-generation sequencing, we can now make appropriate clinical decisions for our patients. Through personalized molecular “biomarker” evaluation, we can now formulate treatment programs for each patient.

Combination therapy
works best

These include low dose targeted metronomic chemotherapy and resistant genes reversal, natural substances, and immunotherapy with checkpoint inhibitors. Immunotherapy with Cancer vaccines including autologous cancer vaccines, dendritic cell vaccines and supportive oligonucleotide therapy (SOT).

If you would like more information on chemotherapy resistance and chemotherapy failure and integrative cancer, please call us at 480-860-2030.

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