HCC70: A model of triple negative breast cancer

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Triple negative breast cancer (TNBC), accounting for 15-20% of all breast cancers, lacks estrogen receptors, progesterone receptors, and amplification or overexpression of Her-2. As such, these tumors are not responsive to hormonal or anti-Her2 therapies, and are usually treated with combinations of surgery, radiation, and chemotherapy. Although many triple negative tumors respond well to chemotherapy, patients generally have poorer prognosis, higher relapse rates with aggressive tumor growth, and high metastatic potential. More than 300 clinical trials are currently ongoing in TNBC (www.clinicaltrials.gov) evaluating various single agent and combination approaches with chemotherapy, targeted therapy, immunotherapy, and radiation therapy. Clinically, radiation therapy has been associated with decreased risk of locoregional recurrence and some instances of improved overall survival when compared to patients that did not receive radiation therapy.1, 2

yaboapp体育官网尿动率较少有临床相关放射治疗方法的效果。Labcorp在房子里有一个小动物辐射研究平台（SARRP; Xstrahl），可以为目前未满足的临床前需要提供解决方案。yaboapp体育官网

HCC70评价紫杉醇和多西紫杉醇

At Covance, the HCC70 human TNBC cell line can be used to model this disease preclinically. This cell line grows well following subcutaneous implant in female NSG mice (Figure 1A). To determine which chemotherapy would be suitable for combination approaches we evaluated both paclitaxel and docetaxel. We observed a strong response to docetaxel and a more modest response to paclitaxel (Figure 1B) with minimal effects on body weight loss (Figure 1C). The response to paclitaxel was further verified in an additional study (data not shown).

HCC70 Response to Radiation

To determine the benefit of paclitaxel in combination with focal radiation, we further employed HCC70 tumor bearing mice to investigate both fractionated (2.5Gy given 5 days on and 2 days off for two cycles) and hypofractionated (8Gy for 3 consecutive days only) radiation treatment plans.

The HCC70 tumor model was sensitive to radiation, and we found that hypofractionated radiation resulted in a slightly improved anti-tumor response with a slightly increased toxicity profile, based on body weight loss (Figures 2A and 2B). However, neither radiation treatment resulted in tumor free survivors, only prolonged tumor stasis based on caliper measurements (Table 1).

Table 1: Endpoint Analysis Following Treatment with Paclitaxel and Focal Radiation

HCC70 Combination Treatment with Radiation and Paclitaxel

当辐射方案与紫杉醇组合时，结果增加了单极的抗肿瘤活性（图2C）。通过治疗分馏辐射和紫杉醇，我们观察到12.5％的肿瘤无幸存者和37.5％的完全回归。这种抗肿瘤活性升至87.5％的肿瘤自由幸存者，利用次规辐射时的87.5％完全回归（表1）。虽然低次处理的处理方法导致额外的治疗益处，但我们确实观察到增加的体重减轻（图2D）。因此，低次级辐射的优点是耐受性较低的成本。

Overview

HCC70 will be a useful model for those looking to interrogate new and novel treatment approaches for TNBC as well as for those looking to combine with paclitaxel and/or radiation therapy. For related information, see our poster:“Focal Radiation Enhances Paclitaxel Therapy in a Mouse Model of Triple Negative Breast Cancer”

接触Labcorpto learn more about our HCC70 model or other breast cancer models that we offer.

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