Low-dose, four-drug combo blocks cancer spread in mice 低劑量，四藥組合可阻止癌症在小鼠中傳播

News Release 11-May-2021

Editor’s note: Often times, oncologists prescribe one anticancer medication at a time. rarely do they use a combo therapy. Combinational therapy make it less likely for cancer cells to survive. The dosage is key. Small doses lead to drug resistance while high doses may kill the patient. Theoretically, it is possible to use a combo therapy to eradicate a cancer.

Vincent T. DeVita Jr. M.D. is probably the first clinical oncologist who used a combinational therapy to treat lymphoma. The method he used is not fool-proof and it requires a lot of skills to get the right doses. And the treatment can be dangerous to the patients as often times, the doses are too high to tolerate. As a result, many cancer patients died during treatment. He tells his unique experience in his book titled the death of cancer.

The dosing method needs to be exact, based on the patient’s disease and his physicals. Unfortunately, no doctors know how to dose exactly. They tend to give the patient the recommended dose regardless of the patient’s physicals.

For that reason, even the combination-al therapy may not work for most cancer patients. Inadequate dosing can fail the treatment and even worse, it can train the cancer cells to be more aggressive.

編者按： 通常，腫瘤科醫生一次開一種抗癌藥。 他們很少使用組合療法。 組合療法使癌細胞存活的可能性降低。 劑量是關鍵。 小劑量會導致耐藥性，而大劑量可能會殺死患者。 從理論上講，可以使用聯合療法根除癌症。 但是，給藥方法必鬚根據患者的疾病及其身體狀況而精確確定。

Vincent T. DeVita Jr. M.D.可能是第一位使用聯合療法治療淋巴瘤的臨床腫瘤學家。 他使用的方法並非萬無一失，並且需要大量技能才能獲得正確的劑量。 而且這種治療對患者來說可能是危險的，通常是因為劑量太高而無法忍受。 結果，許多癌症患者在治療期間死亡。 他在他的《癌症的死亡》一書中講述了自己的獨特經歷。

不幸的是，沒有醫生知道如何精確劑量。 他們傾向於給患者推薦的劑量，而不管患者的身體狀況如何。 因此，即使是聯合療法也可能不適用於大多數癌症患者。 劑量不足會使治療失敗，甚至更糟，它會使癌細胞更具攻擊性。

A new approach to preventing cancer spread that uses a combination of low-dose, metastasis-inhibiting drugs shows promise in mouse studies and may help prevent drug resistance or relapse

eLife

Research News

Low doses of a four-drug combination helps prevent the spread of cancer in mice without triggering drug resistance or recurrence, shows a study published today in eLife.

The findings suggest a new approach to preventing cancer metastasis in patients by simultaneously targeting multiple pathways within a metastasis-promoting network. They may also help identify people who would most likely benefit from such treatment.

Metastasis, the spread of cancerous cells through the body, is a common cause of cancer-related deaths. Current approaches to treating metastatic cancer have focused on high doses of individual drugs or drug combinations to hinder pathways that promote the spread of cancer cells. But these approaches can be toxic to the patient, and may inadvertently activate other pathways that cause the drugs to stop working and the tumours to return.

“There is an urgent need for new strategies to suppress cancer metastasis, especially for cancers such as triple-negative breast cancer that currently lack effective therapies,” says first author Ali Yesilkanal, a postdoctoral scholar at the Ben May Department for Cancer Research at the University of Chicago, US.

In the study, Yesilkanal and colleagues analysed gene expression data from patients participating in the Cancer Genome Atlas study to understand how a metastasis-suppressing protein called Raf Kinase Inhibitory Protein (RKIP) works. They found that RKIP reduces the expression of a network of genes that promote the spread of cancer cells.

They then created a four-drug combination that mimics how RKIP suppresses the ability of cancer cells to spread. They administered low doses of this treatment to mice with metastatic cancer that mimics metastatic breast cancer, and found that it blocked the spread of cancer and increased the animals’ survival. Importantly, the treatment did not trigger the compensatory mechanisms that often cause high-dose, anti-metastasis drugs to stop working and tumours to return.

Finally, the team used computer modelling to explain why reducing, but not completely stopping, the expression of this network of genes helped prevent metastasis without triggering drug resistance or relapse. They also identified patients with breast cancer in the Cancer Genome Atlas who might be most likely to benefit from such treatment based on their cancer’s gene expression patterns.

“Our findings could lead to a new cancer treatment strategy where patients first receive low-dose combination drugs that block metastasis and then receive traditional cancer treatments such as radiation, chemotherapy or immunotherapy,” says co-senior author Marsha Rosner, the Charles B. Huggins Professor at the Ben May Department of Cancer Research at UChicago.

“Our results challenge current approaches to cancer treatment and suggest an alternative strategy for controlling metastasis in breast cancer and potentially other types of cancer,” concludes co-senior author Alexandre Ramos, Group Leader at the School of Arts, Sciences and Humanities, University of São Paulo, Brazil.

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