Conventional cancer treatment modalities are often associated
with
major therapeutic limitations and severe side effects. Photodynamic
therapy is a localized noninvasive mode of treatment that has given
a different direction to cancer research due to its effectivity against
a wide range of cancers and minimal side effects. A photosensitizer
is the key component of photodynamic therapy (PDT) that generates
cytotoxic reactive oxygen species to eradicate cancer cells. As the
therapeutic effectivity of PDT greatly depends upon the photosensitizer,
great efforts have been made to search for an ideal photosensitizer.
Chlorin e6 is a FDA approved second generation photosensitizer that
meets the desired clinical properties for PDT. It is known for its
high reactive oxygen species (ROS) generation ability and anticancer
potency against many types of cancer. Hydrophobicity is a major drawback
of Ce6 that leads to its poor biodistribution and rapid clearance
from the circulatory system. To overcome this drawback, researchers
have designed and fabricated several types of nanosystems, which can
enhance Ce6 solubility and thereby enhance its bioavailability. These
nanosystems also improve tumor accumulation of Ce6 by selectively
targeting the cancer cells through passive and active targeting. In
addition, Ce6 has been employed in many combination therapies like
chemo-photodynamic therapy, photoimmunotherapy, and combined photodynamic–photothermal
therapy. A combination therapy is more curative than a single therapy
due to the synergistic effects of individual therapies. Ce6-based
nanosystems for combination therapies have shown excellent results
in various studies and provide a promising platform for cancer treatment.
Local therapy modalities such as radiation therapy, photodynamic therapy, photothermal therapy, and cryoablation have been used to treat localized tumors for decades. The discovery of the abscopal effect causes a paradigm shift where local therapy also causes systemic effects and leads to the remission of nonirradiated tumors. The abscopal effect of radiation therapy, alone or in combination with other treatments, has been extensively studied over the last six decades. However, the results are unsatisfactory in producing robust, reproducible, and long‐lasting systemic effects. Although immunotherapy and radiation therapy are promising in producing the abscopal effect, the abscopal effect's mechanism is still unclear, owing to various factors such as irradiation type and dose and cancer type. This article reviews the research progress, clinical and preclinical evidence of the abscopal effect by various local therapies alone and in combination with chemotherapy and immunotherapy, case reports, and the current challenges in producing the abscopal effect by various local therapies, focusing on radiotherapy, photodynamic therapy, cryoablation, and the prospects for obtaining a robust, reproducible, and long‐lasting abscopal effect.
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