Mechanisms of Resistance to HER2 Targeted Therapies Sample Clauses

Mechanisms of Resistance to HER2 Targeted Therapies i. Mechanisms of resistance to trastuzumab 28 A. p27/cdk2 30 B. PTEN deficiency/increased Akt activity 34
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Mechanisms of Resistance to HER2 Targeted Therapies i. Mechanisms of resistance to trastuzumab Trastuzumab is an effective treatment in HER2-overexpressing breast cancer, but has limited clinical benefit due to the frequent development of refractory disease within a year. Considerable research has been dedicated to understanding the mechanisms by which trastuzumab resistance develops. In addition to HER2 mediated mechanisms of resistance, the overexpression of the EGFR family members, EGFR, HER3, and HER4, has been linked to trastuzumab resistance. Extensive research has been performed to elucidate the role EGFR plays in the development of trastuzumab resistance, and will be discussed in detail. Also to be discussed in detail is the role of the insulin like growth factor receptor (IGF-IR) in trastuzumab resistance. IGF-IR is not part of the EGFR family, but has been demonstrated to physically interact with HER2 and result in a decreased response to trastuzumab (Lu et al, 2001). Other mechanisms of trastuzumab resistance of importance discussed here will include p27 downregulation, mTOR pathway signaling, and PTEN deficiency/increased Akt activity. Although the mechanisms by which trastuzumab treatment produces anti-cancer effects have not been elucidated, research has revealed that they include:

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  • Screening 3.13.1 Refuse containers located outside the building shall be fully screened from adjacent properties and from streets by means of opaque fencing or masonry walls with suitable landscaping.

  • Human Leukocyte Antigen Testing This plan covers human leukocyte antigen testing for A, B, and DR antigens once per member per lifetime to establish a member’s bone marrow transplantation donor suitability in accordance with R.I. General Law §27-20-36. The testing must be performed in a facility that is: • accredited by the American Association of Blood Banks or its successors; and • licensed under the Clinical Laboratory Improvement Act as it may be amended from time to time. At the time of testing, the person being tested must complete and sign an informed consent form that also authorizes the results of the test to be used for participation in the National Marrow Donor program.

  • Treatment Program Testing The Employer may request or require an employee to undergo drug and alcohol testing if the employee has been referred by the employer for chemical dependency treatment or evaluation or is participating in a chemical dependency treatment program under an employee benefit plan, in which case the employee may be requested or required to undergo drug or alcohol testing without prior notice during the evaluation or treatment period and for a period of up to two years following completion of any prescribed chemical dependency treatment program.

  • Health Screening The Contractor shall conduct a Health Needs Screen (HNS) for new members that enroll in the Contractor’s plan. The HNS will be used to identify the member’s physical and/or behavioral health care needs, special health care needs, as well as the need for disease management, care management and/or case management services set forth in Section 3.8. The HNS may be conducted in person, by phone, online or by mail. The Contractor shall use the standard health screening tool developed by OMPP, i.e., the Health Needs Screening Tool, but is permitted to supplement the OMPP Health Needs Screening Tool with additional questions developed by the Contractor. Any additions to the OMPP Health Needs Screening Tool shall be approved by OMPP. The HNS shall be conducted within ninety (90) calendar days of the Contractor’s receipt of a new member’s fully eligible file from the State. The Contractor is encouraged to conduct the HNS at the same time it assists the member in making a PMP selection. The Contractor shall also be required to conduct a subsequent health screening or comprehensive health assessment if a member’s health care status is determined to have changed since the original screening, such as evidence of overutilization of health care services as identified through such methods as claims review. Non-clinical staff may conduct the HNS. The results of the HNS shall be transferred to OMPP in the form and manner set forth by OMPP. As part of this contract, the Contractor shall not be required to conduct HNS for members enrolled in the Contractor’s plan prior to January 1, 2017 unless a change in the member’s health care status indicates the need to conduct a health screening. For purposes of the HNS requirement, new members are defined as members that have not been enrolled in the Contractor’s plan in the previous twelve (12) months. Data from the HNS or NOP form, current medications and self-reported medical conditions will be used to develop stratification levels for members in Hoosier Healthwise. The Contractor may use its own proprietary stratification methodology to determine which members should be referred to specific care coordination services ranging from disease management to complex case management. OMPP shall apply its own stratification methodology which may, in future years, be used to link stratification level to the per member per month capitation rate. The initial HNS shall be followed by a detailed Comprehensive Health Assessment Tool (CHAT) by a health care professional when a member is identified through the HNS as having a special health care need, as set forth in Section 4.2.4, or when there is a need to follow up on problem areas found in the initial HNS. The detailed CHAT may include, but is not limited to, discussion with the member, a review of the member’s claims history and/or contact with the member’s family or health care providers. These interactions shall be documented and shall be available for review by OMPP. The Contractor shall keep up-to-date records of all members found to have special health care needs based on the initial screening, including documentation of the follow-up detailed CHAT and contacts with the member, their family or health care providers.

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