Editorial: Anakoinosis: An Innovative Anticancer Therapy Targeting the Aberrant Cancer Tissue Homeostasis

Abstract

The aim of anakoinosis is "tissue editing," meaning that bioactive, regulatory acting principles are combined to re-establish tissue homeostasis at primary and metastatic tumor sites by communicatively reprogramming tumor tissue and cell recruitment (Heudobler et al., 2019). Pro-anakoinotic therapies combine regulatorily active drugs, even those with poor or no monoactivity, and may positively supplement classic targeted therapies, as exemplified in relapsed or refractory (r/r) classic Hodgkin's lymphoma (cHL) with the successful introduction of a target of rapamycin (mTor) inhibitor (Heudobler et al., 2018a;.This Research Topic highlights differential clinical outcome characteristics in three histologically completely different neoplasia as a response to "tissue editing" when treated either with pro-anakoinotic approaches (in case of r/r cHL and r/r non-small cell lung cancer, NSCLC) or accidentally initiated by severe fungal infection and reduced intensity induction chemotherapy in acute lymphoblastic leukemia (ALL) (Lüke et al.; Lüke et al.; Heudobler et al.). The clinical responses outline the possibility to specifically activate unique tumor tissue dynamics in response to pro-anakoinotic effectors, either by combining differently acting biomodulatory drugs, or associating DNA damage with fungal infection.DNA damage response following "one shot" chemotherapy in ALL seems to serve as a homeostatic trigger in the case of parallel fungal infection, presumably supervising and amplifying immunological response by the innate immune system, thereby preventing both early relapse and persistence of minimal residual disease, as indicated by long-term continuous complete remission in both described ALL cases (Lüke et al.).In r/r NSCLC, explorative studies of the randomized trial provide strong hints that pre-treatment with combined biomodulatory therapy may be the basis for successful consecutive immune checkpoint inhibitor (ICPi) therapy: even though the progression-free survival rate of the biomodulatory treatment arm is significantly inferior to that of the ICPi arm, it, however, exerts tissue modifications that render successive ICPi more efficacious. These results stimulate the hypothesis that the addition of ICPi to the biomodulation could be beneficial (Heudobler et al.).The immune-modulatory acting MEPED schedule for r/r cHL resulted in pivotal outcomes in six cases. Whether a patient is frail and does not respond to reduced standard first-line therapy, or patients are r/r after autologous hematopoietic-stem-cell transplant (autoHSCT), or even allogeneic

Addressing Genetic Tumor Heterogeneity, Post-Therapy Metastatic Spread, Cancer Repopulation, and Development of Acquired Tumor Cell Resistance

“…As shown, clinical trials using editing approaches may induce long-term tumor control, objective response or even cCR [38] (Figure 1, Table 1). The novel treatment strategy is highly integrative and provides, beyond its biomodulatory activity profile, opportunities for drug repurposing, e.g., by providing edited nononcogene addiction.…”

“…Tumor tissue editing is defined as the therapy-guided targeted evolution of tumor tissues to establish biologic hallmarks that facilitate tumor control or initiate complete remission in relapsed or refractory tumor disease [ 38 ]. Appropriate editing schedules combine bioactive therapeutic principles to readjust aberrant tissue homeostasis at primary and metastatic tumor sites by using differential regulatory active therapeutic techniques [ 39 , 40 ].…”

“…Tumor tissue editing approaches turned out to efficaciously control or resolve M-CRAC by redirecting cancer associated hallmarks into biologic hallmarks, attenuating tumor growth, and inducing alternative patterns of tumor cell death in r/r tumor disease. As shown, clinical trials using editing approaches may induce long-term tumor control, objective response or even cCR [ 38 ] ( Figure 1 , Table 1 ).…”

Unlocking the Potential: Novel NSAIDs Hybrids Unleash Chemopreventive Power toward Liver Cancer Cells through Nrf2, NF-κB, and MAPK Signaling Pathways

“…Therefore, the conjugation of IBU and KET with OAO derivatives may increase their efficacy. Moreover, their potential combined action on the elements of the MAPKs signaling pathway may lead to the anakoinosis effect, which, by targeting the simultaneously different, but cross-talking signaling pathways, is considered an innovative anticancer approach [33].…”