10/25/2022 0 Comments Dead cells progression![]() ![]() Huang explains this counterintuitive paradoxical behavior of tumors with the dictum of philosopher Friedrich Nietzsche: “That which does not kill us makes us stronger.” Unless drug treatment overwhelms the entire tumor – a rarity – it may add fuel to this vicious cycle by causing more tissue destruction in the tumor. Unlike wounded healthy tissues, tumors are wounds that do not heal and regeneration that does not stop. Malignant tumors disrupt normal tissue architecture, which triggers an abnormal regenerative response that is futile and fails to subside. ![]() In Huang’s unifying theory of cancer, this is part of a much broader response. Indeed, it indicates an active counter-response by the tissue to the presence of dead cells and the stress imparted by the treatment: The dead cells cause a local inflammation in the tumor, which is long known to promote cancer. This treatment-stimulated tumor progression suggests a mechanism behind cancer recurrence following initial post-therapy remission that is more complex and sinister than the evolutionary selection and expansion of cells that are naturally drug resistant. ![]() In these tiny tumors, treatment with chemotherapy, or even modern target-selective drugs, resulted in drastic stimulation of tumors that took off like standard aggressive tumors. This setup opened a window to observe the tumor-stimulating effects of treatment. Judah Folkman, question scientific orthodoxy and have created animal models for slow growing or even dormant tumors. In these cases, responses to treatment are either no effect, or a slower growth that implies a drug effect.īut Huang and Panigrahy, drawing lessons of their common mentor at Harvard Medical School and cancer research pioneer, the late Dr. Put another way: Tumor growth can be a byproduct of cancer treatments that kill tumor cells.īut why has this paradoxical effect not previously been observed? Most drug companies and researchers test drugs in animal tumors set up to grow as quickly as possible to mimic aggressive tumors, and to save time and money. More strikingly, cell debris produced by the dying tumor itself as a consequence of cancer treatment, without injection of artificial cell debris, also stimulated tumor growth. But Huang and Panigrahy and their team found that if one co-injects some dead cell debris (generated in the test tube using chemotherapy) alongside tumor cells, then just 1/100 of the number of tumor cells normally used will suffice to generate a tumor that grows as vigorously a tumor as starting with 1 million cells. One way to create tumors in mice for experimental studies and testing drugs is to inject a number of cancer cells into the flank. They repeated the experiments in a variety of mouse tumor models, ranging from lung, pancreas, breast and prostate cancer to melanoma or lymphoma. Huang and Panigrahy showed that such a counterintuitive behavior is actually quite common. This paradoxical response to treatment is not a freak phenomenon. The dead cells trigger a reaction that strengthens the cancer cells that have just escaped death by drugs: These become more like stem cells, which are resilient and robust, and eventually cause recurrence of the tumor. Traditional cancer therapies, then, become a double-edged sword: Too much and too fast, yet incomplete, killing of the tumor cell population will generate so much debris that the tumor stimulatory effect overpowers the decimation of tumor cells. Their findings were published in The Journal of Experimental Medicine on November 30. Dipak Panigrahy at Beth Isreal Deaconess Medical Center in Boston and colleagues at Harvard Medical School, show that dead cells, or cell debris, generated by treatments intended to eradicate tumor cells, actually act as strong stimulators of tumor progression. Sui Huang (pictured above), professor and cancer biologist at Institute for Systems Biology, along with former mentee and longtime collaborator Dr. However, these treatments often fail to eradicate tumors, and cancer often recurs.ĭr. Killing cancer cells is the fundamental objective of chemotherapy, radiation and targeted cancer therapies. ![]()
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