TECHNICAL FIELD

The invention is directed to methods for regenerating non-cancerous tissue in a patient receiving radiation therapy or chemotherapy.

BACKGROUND

The majority of patients diagnosed with cancer will receive irradiation (IR) therapy, either alone or in combination with surgery or chemotherapy. Despite improvements in IR delivery, damage to healthy tissues and the associated morbidities can significantly impact quality of life. Furthermore, IR toxicity, especially in combination with chemotherapy, can limit the course of therapy, potentially impacting tumor eradication in some patients.

In the oral cavity, the oral mucosa and the salivary glands are highly sensitive to IR damage. Up to 40% of patients treated with IR for head and neck carcinoma (HNC) will develop moderate to severe xerostomia as a result of collateral damage to the salivary glands in the IR path. These patients typically experience a reduction in saliva production of >50% within a few weeks of commencing therapy. Salivary gland hypofunction, and the resultant xerostomia, is often permanent and can have a significant impact on oral health and nutrition. Currently, the only therapeutic agent available to protect the salivary gland is the free radical scavenger, amifostine, which is not widely used due to significant toxicity. Thus, there is a need for the development of new therapeutic strategies that will provide selective protection of these radiosensitive normal tissues without impacting tumor cell death.

SUMMARY

The inventors have surprising discovered that administration of a tyrosine kinase inhibitor (TKI) can induce regeneration of non-cancerous tissue injured or killed by a cancer treatment, such as radiation therapy (IR) or chemotherapy, if the TKI is administered continuously to the cancer patient and for at least 10 days, at least 20 days, at least 30 days, at least 40 days, at least 50 days, at least 60 days, at least 70 days, at least 80 days, or at least 90 days, or more following administration of the cancer treatment. These methods are particularly suited to regeneration of salivary gland acinar cells following radiation therapy in a cancer patient. In these methods, the TKIs are useful to regenerate non-tumor tissue, such as salivary gland acinar cells, in cancer patients undergoing radiation therapy without negatively impacting the cancer therapy.

Therefore, one aspect of this disclosure is a method for regenerating non-cancerous cells following a cancer treatment, by administering a therapeutically effective amount of a tyrosine kinase inhibitor (TKI) for several months after administering a cancer treatment to a cancer patient.

In a related aspect, this disclosure provides a method for treating a cancer patient, by administering a tyrosine kinase inhibitor (TKI) to a cancer patient prior to administering a cancer treatment and thereafter continuously administering the TKI to the patient for at least 10-300 days, or for at least 40-250 days, or for at least 70-200 days, or for at least 90-150 days following the administration of the cancer treatment.

In a related aspect, this disclosure provides a method for regenerating non-cancer tissues in a cancer patient, by administering a tyrosine kinase inhibitor (TKI) to a cancer patient prior to administering a cancer treatment and thereafter continuously administering the TKI to the patient for at least 90-150 days following the administration of the cancer treatment.

In any of these aspects, the cancer treatment may comprise radiation therapy.

In any of these aspects, the cancer treatment may comprise chemotherapy.

In any of these aspects, the TKI may be an inhibitor of at least one of Protein Kinase C-delta, c-Abl-, and Src-family kinase.

In any of these aspects, the TKI may be an inhibitor of at least one non-receptor tyrosine kinase.

In any of these aspects, the TKI may be selected from bosutinib, dasatinib, imatinib, nilotinib, pazopanib, ponatinib, sunitinib, and combinations thereof.

In any of these aspects, the cancer may be head and neck cancer, pancreatic cancer, stomach cancer, breast cancer, colon cancer, lung cancer, liver cancer, leukemia, bone cancer, ovarian cancer, cervical cancer, brain cancer, skin cancer, prostate cancer, or thyroid cancer.

In any of these aspects, the TKI may be administered once weekly, or at least twice weekly, or at least 3, 4, 5, 6, or 7 times weekly, or more, following the administration of the cancer treatment.

In any of these aspects, the TKI may be administered continuously for at least 90-150 days following the administration of the cancer treatment.

