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    Diagnosis and treatment of cancer — Case Studies

     


    The following are overviews of some notable recent cases* that exemplify our approach. In all cases, we were able to identify unexpected actionable hypotheses – ideas that pointed to FDA-approved therapies that an oncologist could prescribe or to clinical trials that a patient could enter. These hypotheses are strongly supported by our analyses of the patients' individual diseases and the scientific literature. Our findings have generally been well-received by oncologists. Below we present short overviews of some notable cases.

    Case Study 1: A patient came to us while on Nexavar for large B cell lymphoma. After an initial response to the drug, the cancer had started to accelerate.  We analyzed her cancer tumor and found that while the data supported the use of Nexavar, they also supported the addition of Irinotecan. When Irinotecan was added to her treatment, the tumor stabilized - and remains stable today. We also identified a second mechanism that points to specific clinical trial agents, should the disease start to progress.

    Case Study 2: A male in his 50s was diagnosed with metastatic melanoma. When we examined his tumor, we found two distinct actionable hypotheses. The scientifically stronger one was based on an upregulation of the CDK-2 pathway (combined with a deletion of PKC-eta, a gene that inhibits CDK-2), suggesting a investigational drug (Flavopiridol) that was accruing for a Phase II trial in melanoma. A somewhat weaker hypothesis (fewer corroborating pieces of evidence) was for the SRC and the LCK pathway, which are targets of dasatanib. The patient is currently responding well to his existing therapy, but these approaches remain as a “plan B” in the event that his current treatment stops working. 

    Case Study 3: A 54-year old male suffering from malignant melanoma approached us.  He was being treated by a top melanoma physician/researcher at UCLA. He had previously failed 5 different therapies, and because he had a BRAF mutation, he had enrolled in the PLX4032 trial that had produced excellent, if short term, results for patients with this mutation.  This patient responded to the drug for only 3 months, after which time the tumor progressed and he discontinued the trial.  He was then placed in a trial for a MEK inhibitor (GSK1120212), to which he responded briefly.  With the support of the physician, we were invited to perform an analysis.

    Our analysis of the patient’s tumor suggested that a drug approved for kidney cancer, Sutent, might be appropriate in this case.  The patient’s physician put him on Sutent, and within 2-3 days his abdomen, which had been grossly extended, shrank back to normal size, and the patient was able to eat again. The patient’s sister told us: “Your analysis changed the therapy the oncologist gave my brother.  He praised it for the well-thought through proposal and the unusual thoroughness and depth of the report.  I only wished that we had engaged you earlier so that he could have started Sutent sooner."

    Case Study 4: A male in his 60s with metastatic Non-Small Cell Lung Carcinoma (NSCLC) came to us while partially responding to Avastin. Our analysis suggested that his cancer was driven by two primary pathways: VEGF and PDGF. VEGF is Avastin’s target, which explained the partial response. He was not being treated with a drug targeting PDGF. This suggested that Sutent (which targets both pathways) may be suitable alone or in combination with the Avastin, or Gleevec (which targets PDGF) may be suitable to add to Avastin. Interestingly, while the data indicated a problem with EGFR (a third pathway commonly activated in NSCLC), our analysis concluded that this was not the driving force behind his cancer because there was minimal activity in the rest of the pathway. After presenting this information, we learned that the patient had not responded to Tarceva (a drug that targets EGFR) despite having an EGFR mutation and KRAS unmutated – the personalized medicine “gold standard” that predicts a positive response to Tarceva.


    *From our previous incarnation as the Personalized Oncology Services division of CollabRx.

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