Finding your best treatment option - considering clinical trials

When faced with a diagnosis of ovarian cancer, the goal for many patients is to find the best treatment available.  There may be a good standard of care--that is, a treatment plan the medical profession has determined to be effective in the majority of cases-- that is appropriate for your specific situation and treatment history. However, sometimes the current standard of care is not effective.  Sometimes the standard of care works for a while, but then stops working. Sometimes there is no standard of care for the situation. At these times, participation in a clinical trial may be the best available option.   To be eligible for clinical trials, timing is everything. If you begin treatment without considering trials, you may later find you are ineligible for some trials.

The more women who take part in ovarian cancer clinical trials, the faster we can find better ways to treat the disease. Clinical trials are carefully designed research studies that involve patient volunteers. Clinical trials seek to find ways to improve the medical care and treatment available to women with ovarian cancer.

  Farletuzumab(MORAb-003) 

Unlike most chemotherapy drugs for ovarian cancer, Farletuzumab is a biologic.  Whereas most drugs are made by a chemist, biologics are made by engineered cells.  Biologics are generally large complex molecules and Farletuzumab is no exception. Farletuzumab is an antibody, in many ways very similar to antibodies made naturally in the body.

Farletuzumab has been designed to bind to and block a receptor molecule, called folate receptor alpha (FR-a), which is found on the surface of most ovarian cancer cells. This receptor sits on the surface of the cells of 90% of all ovarian cancers. FR-a is important for the rapid growth and division of tumor cells. Antibody therapeutics such as Farletuzumab can also fight cancer by attracting the immune system to the tumor cells.  Once Farletuzumab binds FR-a on the cell surface, it flags that cell for destruction by immune cells.  By both blocking tumor proliferation controlled by FR-a and attracting the attention of an immune response toward tumor cells, Farletuzumab has dual tumor suppressing actions.

This dual action of Farletuzumab is highly targeted.  Dr. Martin Phillips, the chief medical officer at Morphotek, Farletuzumab's maker, comments that, "If traditional chemotherapy is targeted like a shotgun, antibodies [can be] targeted like a sniper rifle."  The shotgun therapy will potentially hit the tumor target, but it will also hit healthy tissues causing side effects for patients.  The target of Farletuzumab, FR-a, is largely absent from healthy tissue so this antibody will focus its hits on tumor cells almost exclusively. Indeed, early clinical trials demonstrated minimal side effects associated with Farletuzumab.

AMG 479 

The type I insulin-like growth factor receptor  (IGF-IR) expressed on the surface of cells is the target of Amgen's anti-cancer Phase II drug, AMG 479.  Cancer cells may become dependent on the signals provided when the IGF-IR binds to  insulin-like growth factors 1 and 2 (IGF-1 and IGF-2).  When IGF-1 or IGF-2 bind IGF-IR on the cell's surface, a signal is propagated into the cell instructing it to proliferate and assuring its survival. AMG 479 can block IGF-IR signaling by literally blocking the interaction of the receptor with the growth factors.  Deprived of this growth signal, cells stop proliferation and may even go through programmed cell death known as apoptosis. Elwyn Loh, MD/PhD of Amgen explains, "IGF-1R affects survival pathways, which allow cancer cells to survive chemotherapy. Thus combining AMG 479 with chemotherapy is being tested in clinical trials, including ovarian cancer."

AMG 479 is a full human antibody.  Although this therapeutic antibody is made by an engineered cell line, the body cannot distinguish it from those made naturally by the immune system.  Antibodies are known to recognize and bind intruding pathogens with very high affinity and efficiency.  Antibodies generally recognize a very small and specific part of the pathogen known as the epitope.  AMG 479 is an engineered antibody that takes advantage of these normal antibody characteristics.  AMG 479 was selected for its ability not just to bind to IGF-IR, but to bind to the part or epitope of IGF-RI that is involved with interaction of its ligands, the growth factors. Once AMG 479 binds IGF-RI, the docking site for the ligands are no longer available.  The ligands are physically blocked by the antibody from moving into their docking site and so they cannot activate the proliferation and survival signal.  The ability of a therapeutic antibody to alter a biological process within the cell, in this case proliferation and survival, defines it as a functional antibody.

Many functional antibodies are currently being tested in ovarian cancer patients.  They represent an important additional tool in the oncologist's toolbox.  Traditional chemotherapy drugs tend to target basic cellular processes to which most all cells are sensitive, but cancer cells are more sensitive. By contrast, cancer cells may rely on just one or two of a multitude of specific growth pathways including the IGF-RI pathway. Antibodies are highly specific and thus able to target a single pathway. This could eventually allow the oncologist to evaluate which pathways are most critical for a given tumor and then suppress those pathways utilizing functional antibodies. 

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